TY - JOUR. T1 - Adult-onset manifestation of idiopathic T-cell lymphopenia due to a heterozygous RAG1 mutation. AU - Abraham, Roshini S.. AU - Recher, Mike. AU - Giliani, Silvia. AU - Walter, Jolan E.. AU - Lee, Yu Nee. AU - Frugoni, Francesco. AU - Maddox, Daniel E.. AU - Kirmani, Salman. AU - Notarangelo, Luigi D.. PY - 2013/5. Y1 - 2013/5. UR - http://www.scopus.com/inward/record.url?scp=84876890561&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84876890561&partnerID=8YFLogxK. U2 - 10.1016/j.jaci.2012.09.016. DO - 10.1016/j.jaci.2012.09.016. M3 - Article. C2 - 23122631. AN - SCOPUS:84876890561. VL - 131. SP - 1421. EP - 1423. JO - Journal of Allergy and Clinical Immunology. JF - Journal of Allergy and Clinical Immunology. SN - 0091-6749. IS - 5. ER - ...
Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8+ effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia. We demonstrate that transferred T-cells prolong their survival and enhance their memory in lymphopenic mice, in a manner that depends on IL-15 signaling, but not IL-7. We determine that in vitro stimulation of naïve or effector T-cells with IL-7 and IL-15 reduces IL-7Rα, and increases and/or maintains IL-15Rβ expression,
Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8+ effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia. We demonstrate that transferred T-cells prolong their survival and enhance their memory in lymphopenic mice, in a manner that depends on IL-15 signaling, but not IL-7. We determine that in vitro stimulation of naïve or effector T-cells with IL-7 and IL-15 reduces IL-7Rα, and increases and/or maintains IL-15Rβ expression,
TY - JOUR. T1 - T cell homeostasis in tolerance and immunity. AU - Marleau, Annette M.. AU - Sarvetnick, Nora. PY - 2005/9. Y1 - 2005/9. N2 - The size of the peripheral T cell pool is remarkably stable throughout life, reflecting precise regulation of cellular survival, proliferation, and apoptosis. Homeostatic proliferation refers to the process by which T cells spontaneously proliferate in a lymphopenic host. The critical signals driving this expansion are "space," contact with self-major histocompatibility complex (MHC)/peptide complexes, and cytokine stimulation. A number of studies have delineated an association between T cell lymphopenia, compensatory homeostatic expansion, and the development of diverse autoimmune syndromes. In the nonobese diabetic mouse model of type 1 diabetes, lymphopenia-induced homeostatic expansion fuels the generation of islet-specific T cells. Excess interleukin-21 facilitates T cell cycling but limited survival, resulting in recurrent stimulation of T cells ...
Agonists of the sphingosine-1-phosphate (S1P) receptors, like fingolimod (FTY720), are a novel class of immunomodulators. Administration of these compounds prevents the egress of lymphocytes from primary and secondary lymphoid organs causing peripheral blood lymphopenia. Although it is well established that lymphopenia is mediated by S1P receptor type 1 (S1P1), the exact mechanism is still controversial. The most favored hypothesis states that S1P1 agonists cause internalization and loss of the cell surface receptor on lymphocytes, preventing them to respond to S1P. Hence, S1P1 agonists would behave in vivo as functional antagonists of the receptor. For this hypothesis to be valid, a true S1P1 antagonist should also induce lymphopenia. However, it has been reported that S1P1 antagonists fail to show this effect, arguing against the concept. Our study demonstrates that a S1P1 antagonist, W146, induces a significant but transient blood lymphopenia in mice and a parallel increase in CD4+ and CD8+
TY - JOUR. T1 - Parameter identification for model of T cell proliferation in Lymphopenia conditions. AU - Ayoub, Houssein. AU - Ainseba, B. E.. AU - Langlais, M.. AU - Hogan, T.. AU - Callard, R.. AU - Seddon, B.. AU - Thiébaut, R.. PY - 2014/1/1. Y1 - 2014/1/1. N2 - The number of T Lymphocytes (T cells) in the body is under homeostatic control. At equilibrium, the majority of naive T cells are non-dividing and express low levels of the surface protein CD44. In conditions of T cell deficiency (lymphopenia), naive T cells enter into a proliferative phase, undergoing cell division accompanied by a subtle change in their surface expression of CD44. In this study, we use a mathematical modelling approach to analyse the proliferative response of transgenic T cells in lymphopenic conditions. Our nonlinear model is composed of ordinary differential equations and partial differential equations structured by age (maturity of cell) and CD44 expression. To better understand the evolution of CD44 ...
Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, ...
The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naive cells, rapid elimination of effector cells after pathogen clearance, and long-term survival of memory cells. The reduction of T-cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia-induced proliferation and restoration of normal T-cell levels. Such expansion is governed by the interaction of TCR with self-peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL-7. These same ligands, i.e. p/MHC molecules and IL-7, maintain naive T lymphocytes as resting cells under steady-state T-cell-sufficient conditions. Unlike naive cells, typical
Interleukin-7 (IL-7) is an essential cytokine required for the development and maintenance of mature T cell. Its availability is limited under normal conditions, but rises during lymphopenia, leading to increased T cell proliferation. The administration of recombinant IL-7 to normal or lymphopenic mice and humans results in increased T cell numbers and altered T cell phenotype. Hence, IL-7 administration could mediate therapeutic benefits in immunocompromised patients and is currently tested in several clinical trials. However, besides its well-studied effects on T cells little is known about the effect of IL-7 on other immune and non-immune cells and their influence on T cell homeostasis. Therefore, we evaluated the effect of IL-7 therapy on adoptively transferred T cells in IL-7 receptor (IL-7R)-competent and IL-7R-deficient lymphopenic mice. We confirm the benefits of IL-7 therapy on T cell responses but additionally show that many of these effects are dependent on IL-7R expression by host ...
This figure was taken from https://www.nature.com/articles/s41392-020-0148-4#Fig1 and is published under an open access license. The TML was created with the analysis of 12 random death cases, 7 random cases severe infection and 11 random cases of moderate infection. The TML was afterward validated using 90 hospitalized patients. All the patients come from China.. Source : Tan L., Wang Q., Zhang D., et al. (March 27, 2020). Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Nature. https://doi.org/10.1038/s41392-020-0148-4. ...
Induction of lymphopenia has been exploited therapeutically to improve immune responses to cancer therapies and vaccinations. Whereas IL-15 has well-established roles in stimulating lymphocyte responses after lymphodepletion, the mechanisms regulating these IL-15 responses are unclear. We report that cell surface IL-15 expression is upregulated during lymphopenia induced by total body irradiation (TBI), cyclophosphamide, or Thy1 Ab-mediated T cell depletion, as well as in RAG−/− mice; interestingly, the cellular profile of surface IL-15 expression is distinct in each model. In contrast, soluble IL-15 (sIL-15) complexes are upregulated only after TBI or αThy1 Ab. Analysis of cell-specific IL-15Rα conditional knockout mice revealed that macrophages and dendritic cells are important sources of sIL-15 complexes after TBI but provide minimal contribution in response to Thy1 Ab treatment. Unlike with TBI, induction of sIL-15 complexes by αThy1 Ab is sustained and only partially dependent on ...
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Non-HIV related CD4+ lymphocytopenia has been recognised for the last 10 years, but as it probably is not a single nosological entity the exact classification of our patients disease is a matter for discussion. The criteria for the diagnosis of CD4+ lymphocytopenia include: less than 300/μl of CD4+ T cells or less than 20% of the peripheral blood lymphocytes in at least two measurements, no evidence of HIV infection, or other immunodeficiency, and no history of administration of immunosuppressive drugs.1 Both patients fulfilled these criteria.. Clinically, the manifestations of CD4+ lymphopenia range from no symptoms to mild or even opportunistic infections such as histoplasmosis and cytomegalovirus.1 We have found no account of a familial incidence of CD4+ lymphopenia in the literature and suggest that the patients described here may represent a previously unnoticed symptom complex including mental retardation, pansinusitis, bronchiectasis, and warts. Immunologically, they had CD4+ ...
Idiopathic CD4 lymphocytopenia or seronegative hiv or others disease? - posted in -Microbiology and Virology-: Good evening( First ,sorry my poor english ,english is not my mother language. I try my best to describe my illness clearly. On jan,2012, I suddenly fell ill ,it is just fatigue ,weakness,drowsiness,anepithymia.After one weeks,I developed liver damage and i have very deep Urines color like teas for two weeks. On feb,2012, I start severy dry cough,very seve...
Rabbit Polyclonal to FST times after irradiation actually, suggesting that the being rejected of allografts was credited to alloimmune BAPTA tetrapotassium supplier reactions and not really credited to nonspecific radiation-induced damage (Shape 2a). To the effect of Lips on approved allografts using a different lymphodepletion technique, recipients of approved allografts had been treated with Compact disc4- plus Compact disc8-using up antibodies on times 58, 59, and 60 post-transplant (Shape 1b). This treatment also triggered being rejected of the allografts within 55C115 times after antibody treatment (typical success 78 4 times after exhaustion; Shape 1b). Shape 1 Transient lymphopenia qualified prospects to being rejected of cardiac allografts in CB trained recipients Shape 2 Histological exam of typical cardiac grafts in irradiated website hosts To investigate systems root the reduction of approved cardiac allografts in recipients exposed to lymphopenia, we analyzed graft histology at times ...
Not so good! Treatments being given to Relapsing MS patients are increasing their risk of having extremely low levels of white blood cells that are essential to defense of their immune systems.. Multiple sclerosis patients are at risk of developing lymphopenia, or abnormally low levels of immune defense white blood cells, called lymphocytes, according to a study that investigated lymphocyte counts in people with relapsing MS both before and after the start of treatment. The study, "Lymphopenia in treatment-naive relapsing multiple sclerosis," was published in the journal Neurology.. Various therapies are today available to help treat relapsing MS, with the primary goal of regaining function after an attack, preventing new attacks, and, particularly, preventing disability progression. However, as with many other medical treatments, those designed for MS management can cause adverse effects. Some studies have suggested that some medications cause lymphopenia, which is risky in MS because ...
1) Lymphopenia indicates decreased numbers of circulating lymphocytes. It may occur with acute severe disease, some viral diseases (canine distemper, hepatitis, parvovirus and coronavirus infections, feline panleukopenia, FeLV infection), stress-related corticosteroid response, and loss of lymph (2) Loss of lymphocytes, one of the white blood cells. Certain cancer treatments may cause lymphopenia. See also: Lymphocytopenia ICD-9 288.8 DiseasesDB 7677 MeSH D008231 ...
Copyright Disclaimer and notice Publishers Disclaimer The publishers final edited version of this article is available at J Allergy Clin Immunol See additional articles in PMC that cite the published article. was referred to our center with a history of omphalitis and erythroderma in the neonatal period, systemic BCG illness after immunization, and consequently, multiple respiratory infections. Diabetes mellitus was diagnosed at 5 weeks of age. At 8 weeks, he developed severe dyspnea with hypoxia, hepatomegaly and hypothyroidism. Laboratory investigation disclosed agammaglobulinemia, absence of circulating B cells, T cell lymphopenia and neutropenia. Substitute therapy with intravenous immunoglobulins (IVIG) was initiated. At 3 years, he developed generalized lymphadenopathy and a lymph node biopsy showed effaced architecture with lack of follicles, an increased number of CD163+ triggered macrophages and triggered (CD45R0+) T lymphocytes. He continued to have recurrent respiratory infections ...
History of prior cytotoxic, chemotherapeutic, immunosuppressant (e.g., systemic corticosteroids), immunomodulatory (e.g., IL-2, IL-7, interferon-gama), or growth factor therapy within the last 6 months; chemotherapy or immunomodulatory therapy given to treat an underlying disease or condition may be permitted at the protocol teams discretion, provided diagnosis of ICL was established prior to starting this treatment. The treatment has been stable for over 6 months and is being administered at stable doses as maintenance therapy ...
Deficiency in the guanine nucleotide exchange factor dedicator of cytokinesis 8 (DOCK8) causes a human immunodeficiency syndrome associated with recurrent sinopulmonary and viral infections. We have recently identified a DOCK8-deficient mouse strain, carrying an ethylnitrosourea-induced splice-site mutation that shows a failure to mature a humoral immune response due to the loss of germinal centre B cells. In this study, we turned to T-cell immunity to investigate further the human immunodeficiency syndrome and its association with decreased peripheral CD4(+) and CD8(+) T cells. Characterisation of the DOCK8-deficient mouse revealed T-cell lymphopenia, with increased T-cell turnover and decreased survival. Egress of mature CD4(+) thymocytes was reduced with increased migration of these cells to the chemokine CXCL12. However, despite the two-fold reduction in peripheral naïve T cells, the DOCK8-deficient mice generated a normal primary CD8(+) immune response and were able to survive acute influenza
Rabbit Polyclonal to FST times after irradiation actually, suggesting that the being rejected of allografts was credited to alloimmune BAPTA tetrapotassium supplier reactions and not really credited to nonspecific radiation-induced damage (Shape 2a). To the effect of Lips on approved allografts using a different lymphodepletion technique, recipients of approved allografts had been treated with Compact disc4- plus Compact disc8-using up antibodies on times 58, 59, and 60 post-transplant (Shape 1b). This treatment also triggered being rejected of the allografts within 55C115 times after antibody treatment (typical success 78 4 times after exhaustion; Shape 1b). Shape 1 Transient lymphopenia qualified prospects to being rejected of cardiac allografts in CB trained recipients Shape 2 Histological exam of typical cardiac grafts in irradiated website hosts To investigate systems root the reduction of approved cardiac allografts in recipients exposed to lymphopenia, we analyzed graft histology at times ...
Chronic renal failure (CRF) causes immunosuppresion in humans and is thought to be one of the causes of noninfectious secondary immunosuppression in dogs. Hematological, biochemical, and immunological examinations were performed on blood samples obtained from dogs in various stages of CRF. The number of dogs with lymphopenia increased with the progression of clinical signs. All main subsets of lymphocytes were decreased, but more considerable reduction was detected in B-cells, Tc-cells, and NK cells. Depressed lymphocyte response to concanavalin A and pokeweed mitogen was found in dogs with severe clinical signs and lymphopenia. Our results, showing impaired immunological functions, are similar to results obtained from uremic humans, suggesting that infection may be an important complication in dogs with CRF ...
Dweik BAl, Redjoul R, Bastuji-Garin S, Beckerich F, Robin C, Pautas C, Toma A, Cabanne L, Maury S, Cordonnier C Am J Hematol. 2016;91(4):E276-8. ...
Immunologic Effects of Maraviroc in HIV-Infected Patients with Severe CD4 Lymphopenia Starting Antiretroviral Therapy: A Sub-Study of the CADIRIS ...
Hello, I am epicenegreen. I was diagnosed with MS in 1997 after having symptoms since 1996. I took Avonex for less than a year and could not overcome the flu-like symptoms. After another bad vertigo relapse I started Copaxone, which I took until 2015, after a bad relapse in 2014. After steroids for the relapse, I was given Tecfidera, which I took for a year. Due to lymphopenia, I stopped the Tecfidera in May, 2016. I am now looking for a new treatment. My neuro want me to take Rituxan, but was
Lymphocytopenia has been reported to confer adverse outcomes in a number of hematological malignancies. Recently, it has been reported to be associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the incidence of lymphocytopenia at diagnosis in patients with DLBCL, and to confirm its significance as a prognostic factor, particularly in relation to the international prognostic index (IPI). Medical and laboratory records of 165 patients diagnosed with DLBCL were retrieved and analysed. Lymphocyte counts were correlated with overall survival and role as a prognostic marker independent of IPI was determined. Lymphocytopenia (lymphocyte count |or=1x10(9)/L) was noted in 35.8%; it correlated adversely with overall survival (3.4 years vs. 10.3 years, p=0.002). A Cox regression model established that the prognostic significance was independent of the IPI.
TY - JOUR. T1 - Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast cancer. AU - De Giorgi, Ugo. AU - Mego, Michal. AU - Scarpi, Emanuela. AU - Giuliano, Mario. AU - Giordano, Antonio. AU - Reuben, James M.. AU - Valero, Vicente. AU - Ueno, Naoto T.. AU - Hortobagyi, Gabriel N.. AU - Cristofanilli, Massimo. PY - 2012. Y1 - 2012. N2 - Introduction: Lymphocytopenia and circulating tumor cells (CTCs) have been reported as independent prognostic factors for overall survival (OS) in metastatic breast cancer (MBC), and both have been associated with bone metastases. Our objective was to compare the prognostic significance of lymphocytopenia, CTC count, and extensive bone metastases (, 2 lesions) assessed by fluorine-18 (18F) fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with MBC. Patients and Methods: This is a retrospective study that included patients with MBC who were starting ...
The main characteristics of the patients included in this study are shown in Table 1. Tumor histology has been classified according to the World Health Organization (WHO) proposal.16 The majority of the patients received thymectomy and showed an inversion of the CD4+/CD8+ ratio. Five patients were suffering from severe immunodeficiency syndrome characterized by recurrent infections of the lower respiratory tract. Flow cytometry analyses were performed at monthly intervals in the last 6 months, showing a stable reduction of mature CD19+ peripheral cells (unique patient numbers [UPNs] 091, 157, 051, 009, 147). A marked hypogammaglobulinemia had been detected in 4 of the 5 patients, whereas 1 of them (UPN 091) had normal immunoglobulin (Ig) serum levels. On the bases of clinical signs and B lymphopenia, we classified these patients as suffering from Good syndrome. We included in the study also 2 thymoma patients with normal Ig serum levels, normal B-cell counts, and no signs of severe recurrent ...
Incorporating lymphopenia into the Follicular Lymphoma International Prognostic Index (FLIPI) can improve prognostication, according to researchers.
While it would be extremely concerning if the patient in question developed PML while her lymphocyte counts remained at acceptable levels, the facts as now known indicate that this simply was not the case. Given the immunosuppressive properties of Tecfidera, it would appear to be vitally important that patients be regularly tested to check their white blood cell counts. It would seem that the FDA suggestion of once yearly blood tests is insufficient, and I know many neurologists are checking their patients much more frequently, more on the order of at least once every three months. Monitoring for JC virus might make sense if PML were to be seen in Tecfidera patients not experiencing severe lymphopenia, but at this point the available evidence doesnt seem to merit the taking of this extra step. Then again, any extra bit of information is valuable, and Id imagine that some neurologists might Institute testing for JC virus in their Tecfidera patients on their own. Tecfidera is proving to be quite ...
This weeks Neurology Today published a story on PML in patients taking dimethyl fumarate. There have been a total of 4 patients in Europe. Each of the patients had severe and prolonged lymphocytopenia - low lymphocyte counts in their blood. All of them recovered after being taken off fumarates. Severe lympocytopenia occurs in 3% of patients taking fumarates. One of the patients had also been treated with methotrexate, another with steroids. Robert Fox MD interviewed for this story thought that either infection or a significantly altered immune system might be the culprit rather than the fumarate itself. The cause of lymphocytopenia is not yet known, especially since the mechanism of action of fumarates is suppression of oxidative stress, not immunosuppression per se ...
Abnormal haematological variables were common among patients with the new respiratory illness known as SARS, which has had a large impact worldwide.5 Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity. Studies of its effect on various body systems are crucial to the understanding of this disease. Lymphopenia was the most common finding in our study in a cohort of 157 patients with SARS. Postmortem findings showed lymphopenia in various lymphoid organs. We found no features of bone marrow failure or reactive haemophagocytic syndrome. The inflammatory exudates in the lungs showed scanty lymphocytes. In those patients whose lymphocyte subset was analysed, both mean CD4 and CD8 cell counts were low at presentation and fell further during the early course of illness. The patients in this subgroup were young (median age 27 years, range 21 to 58 years) and had no comorbidity. We believe that the low CD4 and CD8 cell counts reflected the severity of infection ...
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Free, official coding info for 2018 ICD-10-CM D72.810 - includes detailed rules, notes, synonyms, ICD-9-CM conversion, index and annotation crosswalks, DRG grouping and more.
Both exogenous commensal and endogenous self antigens stimulate T cell proliferation under lymphopenic conditions. Projects 1 Not started 1 Active 3 Finished. Nimike 1-20 Viittaukset Vuosi Continuous electricity generation from domestic wastewater and organic substrates in a flat plate microbial fuel cell B Min, BE Logan. Mechanism of basophil mediated immune modulation Min, B. Call for Additional Assistance MSTP students and alumni who have completed a PhD with this mentor: Thanks, you are now subscribed Subscribe another email. Type of Doctor Researcher. To find out more full tilt eu our cookies policy, click largest online poker sites. View brettspiel welt erobern of fc liefering futbol24 out of more. Roles of regulatory T cells and gamma delta T cells during chronic inflammatory diseases. In order for the discoveries of Cleveland Clinic physicians and scientists laboratories and investigations futuriti casino auszahlung benefit the public, these discoveries home stud be commercialized in ...
Karen Lambert, Guest Waking Times I have Chronic Fatigue Immune Dysfunction Syndrome (CFS/CFIDS/ME) and HIV-NEGATIVE AIDS, idiopathic CD lymphocytopenia. With these two clinical diagnoses, I believe that makes me living proof that…. ...
Interleukin 7 (IL-7) is a stromal cell-derived cytokine that stands out as being the only cytokine identified to date on which development of B and T lymphocytes is absolutely dependent. IL-7 functions primarily as a growth and antiapoptosis factor for B- and T-cell (alphabeta and gammadelta TCR+ cells) precursors, and is essential for differentiation of gammadelta TCR+ cells. IL-7 can function as a cofactor during myelopoiesis, and is capable of activating monocytes/macrophages and natural killer (NK) cells. Its receptor (IL-7R) is a heterodimer of an alpha chain that specifically binds IL-7 and the common gamma chain gammac that is also a component of the receptors for IL-2, IL-4, IL-9 and IL-15. The functions of IL-7 in normal lymphocyte development and activation have led to the demonstration of the ability of IL-7 to stimulate lymphopoiesis in lymphopenic mice, suggesting a possible clinical application of IL-7 in accelerating lymphoid reconstitution in lymphopenic patients. There have also ...
The immune status of children with malignant disease in remission was assessed usingvarious immune function tests. Children with infections had significantlymore neutropenia, hypogammaglobulinaemia, and impaired cell-mediated immune responses than those without. These two groups combined had much more absolute lymphopenia and impairment of both cell-mediated immunity and antibody-producing capacity thancontrol children with non-malignant conditions. Regular immunological evaluation isrecommended for children with malignant disease when new intensive treatment schedules are under trial and for individual patients particularly prone to develop infections during treatment. ...
Progressive multifocal leukoencephalopathy (PML) is a well recognized demyelinating neurological disorder caused by JC virus. Idiopathic CD4(+) lymphocytopenia (ICL) is a syndrome first described by the Centers for Disease Control and Prevention as a CD4(+) count |300 cells/mm(3) or a CD4(+) coun …
RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Like the previously described patient, our proband also presented with CD4+ T cell lymphopenia, impaired T cell proliferation to mitogens and antigens, reduced NK cell function, and EBV-associated lymphoma. The severity of the disease and the development of EBV lymphoma in both patients suggest that hematopoietic stem cell transplantation should be performed rapidly in patients with RASGRP1 deficiency.
Following Infants with Low Lymphocytes program. As discussed at the 2016 CIS annual meeting, the "Following Infants with Low Lymphocytes: FILLing the Gap registry is now online https://usidnet.org/fill/. The CIS, in collaboration with the United States Immunodeficiency Network and the Jeffrey Modell Foundation have now established a registry to longitudinally collect key clinical and laboratory data, including diagnosis, treatment and outcomes for infants found to have T cell lymphopenia (TCL) as detected by newborn screening using the T cell receptor excision circle assay. This resource will make possible determination of the relative frequency and natural history of TCL as well as the other known causes of low lymphocytes. This registry will collect longitudinal (retrospective and prospective) clinical and immunological data that is already being generated in the course of clinical care to define the status over time of this group of infants and others born with low T cells including the ...
The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal mechanism whereby corticosteroids suppress inflammation is their impeding the access of neutrophils and monocytes to an inflammatory site. Granulocyte function is relatively refractory, whereas monocyte-macrophage function seems to be particularly sensitive to corticosteroids. Corticosteroid administration causes a transient lymphocytopenia of all detectable lymphocyte subpopulations, particularly the recirculating thymus-derived lymphocyte. The mechanism of this lymphocytopenia is probably a redistribution of circulating cells to other body compartments. There is considerable disagreement about the direct effects of corticosteroid administration on human lymphocyte function. The corticosteroid regimen should be adjusted to attain ...
Transplantable or primary murine cancers respond to chemotherapy with anthracyclines or oxaliplatin much more efficiently when they grow in syngenic immunocompetent mice than in immunodeficient hosts (1, 2). Similarly, clinical studies indicate that severe lymphopenia negatively affects the chemotherapeutic response of solid cancers (3), and immune defects are negative predictors of the response to chemotherapy with anthracyclines or oxaliplatin (2, 4, 5). Apparently, some successful chemotherapeutics can induce a type of tumor cell stress and death that is immunogenic (6-8), implying that the patients dying cancer cells serve as a therapeutic vaccine that stimulates an antitumor immune response, which in turn can control residual cancer cells (9, 10). Immunogenic cell death is characterized by the preapoptotic exposure of calreticulin (CRT) on the cell surface (11), postapoptotic release of the chromatin-binding protein high mobility group B1 (HMGB1) (2), and secretion of adenosine ...
In this study, we have clearly shown for the first time that cortisol is as potent as dexamethasone in augmenting CXCR4 expression in vitro at a range of doses comparable to physiological concentration. Our observation strongly suggests that endogenous glucocorticoid induced by exercise or other stressors may modify lymphocyte trafficking by upregulating the level of chemokine receptor CXCR4 on lymphocytes. Regulation of CXCR4 level by endogenous glucocorticoid may therefore be the potential mechanism responsible for postexercise lymphopenia and for dexamethasone-induced lymphopenia. Because elevation of plasma cortisol is not solely induced by exercise but also by various stressors, our observation may be one of the common mechanisms by which stressors modify immune responses.. Modified lymphocyte trafficking dependent on CXCR4 expression may lead to an altered immune response, such as enhancement in delayed-type hypersensitivity (DTH), as shown by Dhabhar and McEwen (11-13). They showed an ...
The discovery of CD25 as a marker of Tregs raised a concern that Tregs may not represent a distinct T-cell lineage, but a particular state of activation, because CD25 is upregulated by all activated T cells. Other highly expressed markers on CD25+ Tregs, including CTLA-4 and GITR, are also upregulated upon activation of T cells. However, adoptive transfer of CD4+CD25+ T cells into lymphopenic mice showed that they proliferate in an MHC-dependent manner and, despite a decline in CD25 expression, their suppressive capacity increases (7). This finding and others spurred an intense exploration of potential genetic mechanisms underlying the differentiation and function of Tregs and a search for a more specific marker of these cells.. These efforts resulted in identification of Foxp3, an X chromosome-encoded member of the forkhead transcription factor family, as a specific marker of Tregs (8-10). Foxp3 was identified as the gene whose loss-of-function mutation is responsible for a disease in mutant ...
The immunity-related GTPases (IRGs) participate in the category of large interferon-inducible GTPases and constitute a cell-autonomous resistance system needed for the control of vacuolar pathogens like in mice. to spontaneous activation from the effector IRG protein when induced by IFNγ. This activation provides cytotoxic consequences producing a serious lymphopenia macrophage flaws and failure from the adaptive disease fighting capability in virulence elements and genetic deviation in the IRG program between different mouse strains correlates with level of resistance and susceptibility to virulent strains. Launch The immunity-related GTPases (IRG proteins previously known as p47 GTPases) had been first referred to in the 1990s as genes highly induced by disease via interferon gamma (IFNγ) (also to a lesser degree by type I IFN) in mice (Boehm et al. 1998; Carlow et al. 1995; Wall and Gilly 1992; Lafuse et al. 1995; Sorace et al. 1995; Taylor et al. 1996). Targeted deletions pioneered by ...
Results: 16 pts enrolled from 12/05-4/07. Median age 59.5 yrs (range 47-79). 13 females (81%). PS 0:1, 10 pts (63%):6 pts (37%). Fifteen of 16 pts had only 1 prior cytotoxic regimen; 1 pt had only prior erlotinib. Best response to prior treatment: partial response (1 pt), stable disease (SD; 12 pts), progressive disease (PD; 3 pts). Median time since last prior therapy: 2.7 mo (range 0.2-78.5). Vorinostat treatment compliance: 96.3 %. Two pts were not evaluable for response due to not completing Cycle 1 of treatment due to PD. No objective antitumor responses were seen in the first 14 evaluable pts. Eight pts experienced SD (median 3 mo, range 1.7-10.7). Median TTP: 2.4 mo (range 0.9-17.9+); median OS 6.5 mo (range 1.4-17.9+); estimated 6 mo OS rate 54% (SE 13%) and estimated 1 year OS rate 18% (SE 11%). Adverse events possibly or probably related to vorinostat: Grade (Gr) 5 toxicity: CVA (1 pt). Gr 3/4 toxicities: neutropenia (Gr 4-1 pt; Gr 3-1 pt), lymphopenia (Gr 3-3 pts), fatigue (Gr 3-2 ...
Alemtuzumab is a highly efficacious therapy used in the treatment of multiple sclerosis (MS), but uncoupling of T and B cell repopulation during immune reconstitution associates with an increasing range of secondary B cell-mediated autoimmune complications. A 34-year-old woman developed Graves disease 11 months following an initial course of alemtuzumab treatment for MS. Nine months following the second treatment with alemtuzumab, the patient presented with spontaneous intramuscular and subcutaneous haemorrhage due to development of an inhibitory autoantibody to coagulation factor VIII. Acquired haemophilia A (AHA) is an extremely rare complication in patients treated with alemtuzumab. Treatment with rituximab may induce a rapid remission of AHA; however, the patients high John Cunningham virus (JCV) antibody index and alemtuzumab-induced T cell lymphopenia may lead to an increased risk of progressive multifocal leucoencephalopathy, a potential complication which was unacceptable to the ...
The Wiskott Aldrich syndrome protein is an essential cytoskeleton regulator found in cells of the hematopoietic lineage and controlling the motility of leukocytes. The impact of WAS gene deficiency on the mobilization of hematopoietic progenitor/stem cells in circulation has remained unexplored but information would be pertinent in the context of autologous gene therapy of the Wiskott Aldrich syndrome disease. The response to granulocyte-colony stimulating factor mobilization was investigated in a murine WAS knock-out model of the disease, by measuring haematological parameters, circulation and engraftment of hematopoietic progenitor/stem cells. In the steady-state, adult WAS knock-out mice have B cell lymphopenia, marked neutrophilia, increased counts of circulating haematopoietic progenitor cells and a splenomegaly presumably caused by the retention of hematopoietic progenitor cells due to high levels of splenic CXCL12. In spite of these anomalies, the administration of granulocyte-colony ...