Development of long-lived humoral immunity is dependent on CXCR5-expressing T follicular helper (Tfh) cells, which develop concomitantly to effector Th cells that support cellular immunity. Conventional dendritic cells (cDCs) are critical APCs for initial priming of naive CD4+ T cells but, importantly, also provide accessory signals that govern effector Th cell commitment. To define the accessory role of cDCs during the concurrent development of Tfh and effector Th1 cells, we performed high-dose Ag immunization in conjunction with the Th1-biased adjuvant polyinosinic:polycytidylic acid (pI:C). In the absence of cDCs, pI:C failed to induce Th1 cell commitment and IgG2c production. However, cDC depletion did not impair Tfh cell differentiation or germinal center formation, and long-lived IgG1 responses of unaltered affinity developed in mice lacking cDCs at the time point for immunization. Thus, cDCs are required for the pI:C-driven Th1 cell fate commitment but have no crucial accessory function ...
Follicular helper CD4 T (Tfh) cells are a distinct type of differentiated CD4 T cells uniquely specialized for B cell help. In this study, we examined Tfh cell fate commitment, including distinguishing features of Tfh versus Th1 proliferation and survival. Using cell transfer approaches at early time points after an acute viral infection, we demonstrate that early Tfh cells and Th1 cells are already strongly cell fate committed by day 3. Nevertheless, Tfh cell proliferation was tightly regulated in a TCR-dependent manner. The Tfh cells still depend on extrinsic cell fate cues from B cells in their physiological in vivo environment. Unexpectedly, we found that Tfh cells share a number of phenotypic parallels with memory precursor CD8 T cells, including selective upregulation of IL-7Rα and a collection of coregulated genes. As a consequence, the early Tfh cells can progress to robustly form memory cells. These data support the hypothesis that CD4 and CD8 T cells share core aspects of a memory ...
Several experiences induced us to consider genital HPV infection as an expression of a local immunodeficiency. The aim of our study was to research the effect of immunotherapy on the lymphocyte subpopulations and Langerhans cells in vulvar condyloma. Twenty women with persistent vulvar condylomata, treated with 2,000,000 IU/die of beta-interferon for 15 days, were submitted to vulvar biopsy before and 2-5 months after medical treatment. The frozen sections obtained were assayed with the following monoclonal antibodies: OKT4 (T helper lymphocytes), OKT8 (T suppressor lymphocytes), OKB7 (B lymphocytes) and S-100 protein (Langerhans cells). Using a morphometric evaluation, the average number of both intraepithelial and stromal lymphocyte subsets and of the intraepithelial Langerhans cells was assessed. In all the biopsies preceding the medical treatment we found a low number of T helper lymphocytes both in the epithelium and stroma, with inversion of T4/T8 lymphocyte ratio and rare presence of ...
We recently observed a very weak type I (IFN-α/β) ISG response in two chimpanzees with acute hepatitis A (Lanford et al., 2011). The present study was undertaken to assess cellular immunity in the setting of weak ISG activity, and to define protective mechanisms that contribute to resolution of acute symptomatic hepatitis A and prevent relapse of liver disease that is observed in some individuals after apparent control of the infection. Our results indicate that control of acute hepatitis A was most closely associated with a CD4+ T cell response that was strong and sustained despite weak ISG activity.. Control of HCV and HBV infections is critically dependent on CD8+ T cells. Studies in humans and chimpanzees have documented a temporal association between the development of a functional CD8+ T cell response and control of liver infection (Rehermann, 2009; Chisari et al., 2010; Walker, 2010). Moreover, infection is prolonged or persists in HCV and HBV-infected chimpanzees after ...
Several elegant models of AAD have been described whereby transfer of in vitro-polarized Th2 cells induces pulmonary eosinophilia 18,19,20,21. However, the Th cells used for these studies were, in general, polarized for short times in culture. Therefore, we set out to develop a system whereby Th cells were maximally polarized to ensure differential chemokine receptor expression, and thus induced multiple pathophysiological endpoints after transfer in vivo. Th2 or Th1 cells were generated in vitro after several rounds of polarizing cytokines before transfer in vivo, when mice received multiple serial in vivo antigen challenges. Accordingly, Th1 or Th2 cells were transferred intravenously to unsensitized BALB/c recipient mice, and changes in lung function were measured at various time intervals after antigen challenge. Mice were then killed at day 4 or 7, and the extent of inflammation was determined in the BAL and tissue (Fig. 1). Control mice that received cells but no antigen challenge showed ...
T helper cell factors (HF) have been preparated against protein and synthetic antigens by restimulating in vitro induced helper cells with small amounts of antigen. HF when tested in vitro are antigen specific and capable of replacing T cells, initiating a thymus dependent IgM response. In the in vivo adoptive transfer assay HF is capable of replacing T helper cells and is active at very high dilution, inducing both IgM and IgG responses. When tested on unirradiated DNP primed animals the HF was able to initiate a thymus dependent anti-hapten response, comparable to that seen with helper T cells, of both IgM and IgG class. It was also shown that HF acts on anti-Thy 1 treated spleen cells. The results indicate that antigen specific helper factors may be one of the physiologic mediators of T-B interactions in intact animals.
An overview chapter discussing extracellular nucleotides, in particular ATP, and its complex effects and regulation of immune responses & inflammatory reactions
CD4+ T cells are critical for host defense but are also major drivers of immune-mediated disease. These T cells specialize to become distinct subsets and produce restricted patterns of cytokines, which are tailored to combat various microbial pathogens. Although classically viewed as distinct lineages, recent work calls into question whether helper CD4+ T cell subsets are more appropriately viewed as terminally differentiated cells or works in progress. Herein, we review recent advances that pertain to this topic and the mechanisms that contribute to helper CD4+ T cell commitment and plasticity. The therapeutic implications of these new findings are also considered.. ...
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The follicular helper T (Tfh) cells help is critical for activation of B cells, antibody class switching and germinal center formation. The Tfh cells are characterized by the expression of CXCR5, ICOS, PD-1, Bcl-6, and IL-21. They are involved in clearing infections and are adversely linked with autoimmune diseases and also have a role in viral replication as well as clearance. Tfh cells are generated from naïve CD4 T cells with sequential steps involving cytokine signaling (IL-21, IL-6, IL-12, activin A), migration and positioning in the germinal center by CXCR5, surface receptors (ICOS/ICOSL, SAP/SLAM) as well as transcription factor (Bcl-6, c-Maf, STAT3) signaling and repressor miR155. On the other hand Tfh generation is negatively regulated at specific steps of Tfh generation by specific cytokine (IL-2, IL-7), surface receptor (PD-1, CTLA-4), transcription factors Blimp-1, STAT5, T-bet, KLF-2 signaling and repressor miR 146a. Interestingly, miR 17-92 and FOXO1 acts as a positive as well as a
Methods to prime human CD4+ T cells in vitro would be of significant value for the pre-clinical evaluation of vaccine candidates and other immunotherapeutics. However, to date, there is no reliable method for the induction of primary human T cell responses in the laboratory. Here, we optimized a culture strategy incorporating highly purified lymphocytes and dendritic cells, in the absence of any exogenous growth factors, for the in vitro sensitization of naïve CD4+ T cells against a variety of protein antigens. This fully autologous approach, which was superior to the more traditional PBMC assay for supporting the induction of primary human T helper cell responses in culture, elicited effector cells capable of producing a variety of Th cytokines, including IFN?, TNFa, IL-2, IL-5, IL-17 and IL-21, and memory cells that could be restimulated multiple times with a specific antigen. Through simple modifications to this culture method, we evaluated the role of dendritic cell maturation state and ...
The lymphoid follicle is critical for the development of humoral immune responses. Cell circulation to this site is highly regulated by the differential expression of chemokine receptors. This feature contributes to the establishment of viral reservoirs in lymphoid follicles and the development of some types of malignancies that are able to evade immune surveillance, especially conventional CD8+ T cells. Interestingly, a subtype of CD8+ T cells located within the lymphoid follicle (follicular CD8+ T cells) was recently described; these cells have been proposed to play an important role in viral and tumor control, as well as to modulate humoral and T follicular helper cell responses. In this review we summarize the knowledge on this novel CD8+ T cell population, its origin, function and potential role in health and disease, in particular, in the context of the infection by the human immunodeficiency virus.
TY - JOUR. T1 - Peptide epitope identification for tumor-reactive CD4 T cells. AU - Kobayashi, Hiroya. AU - Celis, Esteban. PY - 2008/4/1. Y1 - 2008/4/1. N2 - Because T lymphocytes have the capacity to recognize tumor cells, significant efforts are being devoted towards the development of T cell-based immunotherapy for cancer. Most of this work has centered in the induction of anti-tumor CD8 T cells, which exhibit cytolytic activity towards tumor cells expressing tumor-specific or tumor associated antigens. Unfortunately to this day, T cell-based immunotherapy for cancer remains suboptimal. One of the possible explanations is that these immunotherapies have ignored the role that CD4 T helper lymphocytes play in the generation and persistence of CD8 T cell responses. Thus, we believe that in order to obtain clinical benefits T cell-based immunotherapy must stimulate both CD8 and CD4 tumor-reactive T cell responses. During the past seven years our group has focused on the identification of CD4 T ...
T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Here, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class II-restricted epitopes, we found that myosin heavy chain α (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in Balb/c mice. Transferred MYHCA614-629-specific CD4+ T cells (TCR-M cells) selectively accumulated in the myocardium and mediastinal lymph nodes (med-LNs) of infarcted mice, acquired a Treg phenotype with a distinct prohealing gene expression profile, and mediated cardioprotection. Myocardial Tregs were also detected in autopsy samples from patients who had had a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in patients with MI. Notably, the med-LN alterations ...
The pathophysiology of AIDS is complex, as is the case with all syndromes. Ultimately, HIV causes AIDS by depleting CD4+ T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases. During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells accounts for CD4+ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers. Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4+ T cell loss occurs during the first weeks of ...
The pathophysiology of AIDS is complex, as is the case with all syndromes. Ultimately, HIV causes AIDS by depleting CD4+ T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases. During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells accounts for CD4+ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers. Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4+ T cell loss occurs during the first weeks of ...
A team of Whitehead Institute researchers recently discovered how T follicular helper cells function in the body, a key to understanding the human immune system.
BACKGROUND: CD40 is a 48 kDa type I transmembrane protein that is constitutively expressed on hematopoietic cells such as dendritic cells, macrophages, and B cells. Engagement of CD40 by CD40L expressed on T cells results in the production of proinflammatory cytokines, induces T helper cell function, and promotes macrophage activation. The involvement of CD40 in chronic immune activation has resulted in CD40 being proposed as a therapeutic target for a range of chronic inflammatory diseases. CD40 antagonists are currently being explored for the treatment of autoimmune diseases and several anti-CD40 agonist mAbs have entered clinical development for oncological indications. RESULTS: To better understand the mode of action of anti-CD40 mAbs, we have determined the x-ray crystal structures of the ABBV-323 (anti-CD40 antagonist, ravagalimab) Fab alone, ABBV-323 Fab complexed to human CD40 and FAB516 (anti-CD40 agonist) complexed to human CD40. These three crystals structures 1) identify the ...
Cell-mediated immune responses to HCV antigens may play a role in the pathogenes is of chronic liver disease, viral persistence, and treatment outcome in patients with HCV infection. Observations suggest that CD8 + T cells may be critical for successful HCV clearance. Continue reading "HCV Clearance: IFN Treatment and T Helper Cell Response" →. ...
The invention discloses methods for inducing a desired T helper lymphocyte regulated immune response by delivering an immunogen to a preselected region of the gastrointestinal tract of a subject. The
If you have a question about this talk, please contact Danielle Stretch.. Gene expression levels are believed to be continuously distributed from very low to very high levels, with most genes at an intermediate level. We have studied the transcriptome-wide distribution of expression levels in mouse T helper cells using RNA -seq technology, and have developed a variety of ways to model the expected background levels. This is critical for definition of a threshold level of expression of a gene in a given cell type. In order to calibrate the RNA -seq expression levels in terms of molecules of mRNA per cell, we have intregrated the RNA -seq data with single molecule mRNA-FISH experiments.. The results of these analyses and experiments show that many genes are expressed at > ~1 molecule per cell and that two major expression levels can be identified which vary by roughly one to two orders of magnitude. This gives rise to bimodal distributions of gene expression levels in cell populations. Analysis of ...
Hi and welcome to the forum! I am glad that I can help you.You would like to know whether you are at risk of being infected with HIV although you received a negative HIV test 5 months and a week after the suspicious event.HIV causes weakening of the immune system by affecting the T helper lymphocytes leading to a cond
Ac-Choline Receptor Alpha1 (129-145) (Human, Bovine, Mouse, Rat), 10 mg. This fragment of a conserved sequence in nicotinic acetylcholine receptor activates T helper lymphocytes and induces the production of autoantibodies that cause electrophysiologic
T helper cells (also known as effector T cells or Th cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that play an important role in establishing and maximizing the capabilities of the immune system. .   they have no cytotoxic or phagocytic activity; they cannot kill infected host (also known as somatic) cells or pathogens, Th cells are involved in activating and directing other immune cells, and are particularly important in the immune system .  Mature Th cells are believed to always express the surface protein CD4. T cells expressing CD4 are also known as CD4+ T cells. .  Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells (associated with MHC class I), since they express the CD8 glycoprotein at their surface. Through SLOB[ clarification needed] interaction with T regulatory CD4+CD25+FoxP3+ cells, these cells can be ...
To make the video memorable, it has to feel like a journey and have a punch line at the end - a complete story arc or a loop of information. Thus, I think it would be best to present a threat in the beginning then focus on the roles of B-Cells and use them as the story driver: The audience needs a reason to go on a journey so the B-Cells could be presented in a way that feels as if they are "waiting for activation" by the Helper T-Cells and their Cytokines. (Cytokines are proteins that "stimulate the other cells to be more active") The film will move on to show what is keeping the Phagocytes busy and how they then interact with Helper T-Cells. The explanation of the exact roles of Helper T-Cells would lead back to the activation of the B-Cells and the 3/4 change of pace of the video. A final illustration of the battle between this whole system and the pathogen presents itself as a satisfying conclusion for our story arc ...
The mammalian Signal Transducer and Activator of Transcription (STAT) family members is composed of 7 users (1, 5a, 5b and 6). STAT molecules exert essential
In response to antigen presentation, helper T lymphocytes (TH cells) initiate store-operated Ca2+ entry (SOCE) and differentiate into effector subtypes such as TH1 and TH2 cells. These cells play essential roles in adaptive immunity and the pathogenesis of various autoimmune and allergic diseases. The differentiation and activity of TH cells are also critically regulated by paracrine and autocrine soluble factors in the cell microenvironment. Previous studies have reported that TH cells produce gamma-aminobutyric acid (GABA) via glutamic acid decarboxylase (GAD) and express A-type GABA receptors (GABAARs), forming an autocrine GABA signaling system. In addition, GABA executes anti-inflammatory actions in TH1-autoimmune diseases. This project sought to examine whether autocrine GABA signaling distinctively regulates the function of different TH effector cells using two unique lines of human TH cells: Jurkat and CCRF-CEM. Our results showed that Jurkat and CCRF-CEM cells exhibited features of TH1 and TH2
CD4+ T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging.
4 ± 88.4 (log10 2.45 ± 1.95). YC-Brij700chitosan-gp140 but not YC-SDS-gp140 nor YC-NaMA-gp140 promoted significant specific-gp140 IgA titers (P < 0.05) after three immunizations (90 days). Such effect was comparable to that of Alum at the same time point (P < 0.05). However, the effect of NP as a whole on serum specific-gp140 IgA after i.d. immunization was low because the kinetics and magnitude of specific-gp140 IgA responses promoted by Alum after the first boost (60 days) was significantly superior to those of NP ( Fig. 4C). To test whether YC-wax NP modulated T-helper cell responses, the gp140 specific IgG1/IgG2a. ratio was also determined by ELISA. Of note, gp140 alone induced an IgG response that was biased selleck screening library towards a Th2 phenotype. Such a response did not appear to be modulated by Alum, YC-wax NaMA or YC-wax Brij700-chitosan (Fig. 4D). However, YC-wax SDS appeared to induce a more balanced Th1/Th2 response. (Fig. 4D). To test whether NP were also capable of ...
2016 Mar 17 doi 1111/all.12887 (epub ahead of print).. OMahony L, Akdis CA, Eiwegger T. Innate mechanisms can predict successful allergy immunotherapy. J Allergy Clin Immunol. 2016 Feb, 137(2):559-61.. Christiansen A, Kringelum JV, Hansen CS, Bogh KL, Sullivan E, Patel J, Rigby NM, Eiwegger T, Szepfalusi Z, de Masi F, Nielsen M, Lund O, Dufva M. High-throughput sequencing enhanced phage display enables the identification of patient-specific epitope motifs in serum. Sci Rep 2015; 5: 12913.. Soyka MB, Holzmann D, Basinski TM, Wawrzyniak M, Bannert C, Bürgler S, Akkoc T, Treis A, Rückert B, Akdis M, Akdis CA, Eiwegger T.. The induction of IL-33 in the sinus epithelium and its influence on T-helper cell responses. PlosOne 2015; 10: e0123163.. Boyman O, Kaegi S, Akdis S, Bavbek S, Bossios A, Chatzipetrou A, Eiwegger T, Firinu D, Harr T, Knol E, Matucci A, Palomares O, Schmidt-Weber C, Simon HU, Steiner UC, Vultaggio A, Akdis CA and Spertini F. EAACI IG Biologicals task force paper on the use of ...
Biology Animations includes selected, high quality biological animations; about cell biology, microbiology, genetics, immunology, cancer treatments and diagnosis.... ...
Hatzi K, J Nance P, Kroenke MA, Bothwell M, Haddad EK, Melnick A, Crotty S. 2015. BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms.. J Exp Med. 212(4):539-53. ...
Results: Mean IL-4R expression on monocytes and Th lymphocytes did not differ at birth. After one year it increased on Th-lymphocytes and decreased on monocytes. However, among 10 children with severe atopy during the observation period, 8 displayed IL-4R above the mean value for the group on both monocytes and Th cells at birth as well as one year later. No correlation was found between IL-4 or IFN-γ and IL-4R expression at birth. After one year, significant IL-4 increases and IFN-γ decreases were observed which correlated with IL-4R expression. IL-4R expression on the newborns monocytes correlated negatively with IL-12 plasma level; however, it was statistically significant only in the children developing allergy. Moreover, only in these patients was a significant decrease in IL-12 found after one year ...
R. A. Maldonado, Soriano, M. A., L. Perdomo, C., Sigrist, K., Irvine, D. J., Decker, T., and Glimcher, L. H., "Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse", Journal of Experimental Medicine, vol. 206, no. 4, pp. 877 - 892, 2009. ...
Pawelec, G.; Brocker, Thomas; Busch, Friedrich W.; Bühring, Hans-Jörg; Fernandez, N.; Schneider, E. M. und Wernet, P. (1988): "Tolerization" of human T-helper cell clones by chronic exposure to alloantigen. Culture conditions dictate autocrine proliferative status but not acquisition of cytotoxic potential and suppressor-induction capacity. In: The Journal of Molecular and Cellular Immunology, Vol. 4, Nr. 1: S. 21-34 [PDF, 2MB] ...
a cytokine released by monocytes, macrophages and other immune cells that fight infection. IL-1 activates helper T-cells, mediates acute systemic immune symptoms (e.g., fever) and acts on the hypothalamus to decrease appetite ...
CD4, 50 µg. The CD4 antigen is highly expressed on human T helper cells and thymocytes, and at lower levels on monocytes and dendritic cells.
that prosecutes therapeutic technology. It is a class of technology that allows the T helper cells in the body to recognize cancer in their bodies. When the T helper cells in the immune system of the body are trained to recognize the cancer cells, it kills the cancer cells. This technology is going to be extremely important for patients that are undergoing surgery. There are still loose cells of the tumor traveling through the body and it is very difficult to detect and kill them with chemotherapy. The best way is to use our technology in a therapeutic format. Patients with breast cancer and other cancers could expect in using our technologies, to be able to see a much higher survival rate. Presently we are in the clinic with this technology and we are dosing patients and we are hoping that in the next six months we will be ready ...
T-rakud, mis reageerides makrofaagide poolt eksponeeritavale antigeenile, stimuleerivad B- ja T-lümfotsüüte, et neist areneksid vastavalt antikehasid moodustavad plasmarakud ja tapja-T-rakud.. ...
Two synergizing antigen-specific helper T (Th) cell populations are required for an optimal TEPC15 (T15)-dominated antiphosphorylcholine (PC) plaque- forming cell response . In these studies, the two Th cell sets are shown to differ in their requirements for recognition of self-major histocompatibility complex (MHC)-encoded determinants by testing the ability of Th cells from F(1) {arrow} parent bone marrow chimeras to collaborate with PC-specific B cells bearing MHC-encoded determinants of either parental haplotypes. Previous studies have shown that one antigen-specific Th cell population is required for T-dependent anti-PC responses and activates PC-specific B cells only if the hapten, PC, is physically linked to the priming antigen. This Th cell, referred to as ThMHC, induces anti-PC responses that are mainly non-T15 in character, and it appears to be identical to the conventional antigen- specific Th cell. In these experiments, using T cells from (A X B)F(1) {arrow} parent A chimeras, ThMHC ...
Immunoglobulin E (IgE) is a type of antibody associated with allergies and response to parasites such as worms. When high-affinity, allergen-specific IgE binds its target, it can cross-link receptors on mast cells that induce anaphylaxis. It remains unclear, however, how B cells are instructed to generate high-affinity IgE. Gowthaman et al. discovered a subset of T follicular helper cells (TFH13) that direct B cells to do just that. TFH13 cells are induced by allergens but not during parasite infection. Transgenic mice lacking these cells show impaired production of high-affinity, anaphylactic IgE. TFH13 cells, which are elevated in patients with food and aeroallergies, may be targeted in future antianaphylaxis therapies.. Science, this issue p. eaaw6433 ...
Follicular T helper (Tfh) cells are essential in the formation of high-affinity antibody producing plasma cells and memory B cells. After antigen encounter naive Tfh cells start to upregulate the chemokine receptor CXCR5. This results in homing of the Tfh cells to lymph node follicles where the Tfh cells specifically ... read more localise in germinal centres (GCs). In the GCs the Tfh cells stimulate B cells to differentiate resulting in the production of antibodies. In systemic lupus erythematosus (SLE) an increased amount of autoantibodies is seen. Recent studies postulate that an increased amount of autoantibodies can be related to Tfh cells. The exact role of Tfh cells in the production of autoantibodies in SLE remains elusive, but some research papers provide information from which potential roles can be drawn. The essence of these research papers is the increased level of the chemokine ligand CXCL13 in SLE. CXCL13 levels correlate with disease severity. Further knowledge concerning the ...
TY - JOUR. T1 - Combination peptide immunotherapy suppresses antibody and helper T cell responses to the major human platelet autoantigen GPIIb/IIIa in HLA-transgenic mice. AU - Hall, Lindsay S. AU - Lennon, Charlotte S. AU - Hall, Andrew M. AU - Urbaniak, Stanislaw J.. AU - Vickers, Mark A. AU - Barker, Robert N. N1 - The study was funded by grants from the Medical Research Council (UK) Confidence in Concept, the Scottish National Blood Transfusion Service and the Wellcome Trust (UK). PY - 2019/5. Y1 - 2019/5. N2 - Platelet destruction in immune thrombocytopenia is caused by autoreactive antibody and T cell responses, most commonly directed against platelet glycoprotein IIb/IIIa. Loss of self-tolerance in the disease is also associated with deficient activity of regulatory T cells. Having previously mapped seven major epitopes on platelet glycoprotein IIIa that are recognised by helper T cells from patients with immune thrombocytopenia, the aim was to test whether peptide therapy with any of ...
Follicular helper T cells (Tfh) represent a distinct subset of CD4+ T cells specialized in providing help to B lymphocytes. Studies have indicated that Tfh in circulating blood can act as a prognostic marker for diseases. In the current study, we inv
Wong, M.T., Chen, J., Narayanan, S. et al.. Single-cell analysis technologies such as mass cytometry allow for measurements of cellular heterogeneity with unprecedented dimensionality. Here, we applied dimensionality reduction and automated clustering methods on human T helper (TH) cells derived from peripheral blood and tonsils, which showed differential cell composition and extensive TH cell heterogeneity. Notably, this analysis revealed numerous subtypes of follicular helper T (TFH) cells that followed a continuum spanning both blood and tonsils. Furthermore, we identified tonsillar CXCR5loPD-1loCCR7lo TFH cells expressing interferon-γ (IFN-γ), interleukin-17 (IL-17), or Foxp3, indicating that TFH cells exhibit diverse functional capacities within extrafollicular stages. Regression analysis demonstrated that CXCR5loPD-1(-) and CXCR5loPD-1lo cells accumulate during childhood in secondary lymphoid organs, supporting previous findings that these subsets represent memory TFH cells. This study ...
A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for ...
Gonorrhea is one of the most prevalent sexually transmitted diseases in the world. A naturally occurring variation of the terminal carbohydrates on the lipooligosaccharide (LOS) molecule correlates with altered disease states. Here, we investigated t
TY - JOUR. T1 - FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients. AU - Cencioni, M. T.. AU - Santini, S.. AU - Ruocco, G.. AU - Borsellino, G.. AU - De Bardi, M.. AU - Grasso, M. G.. AU - Ruggieri, S.. AU - Gasperini, C.. AU - Centonze, D.. AU - Barilá, D.. AU - Battistini, L.. AU - Volpe, E.. PY - 2015/5/1. Y1 - 2015/5/1. N2 - Functionally distinct T-helper (Th) subsets orchestrate immune responses. Maintenance of homeostasis through the tight control of inflammatory Th cells is crucial to avoid autoimmune inflammation. Activation-Induced Cell Death (AICD) regulates homeostasis of T cells, and it has never been investigated in human Th cells. We generated stable clones of inflammatory Th subsets involved in autoimmune diseases, such as Th1, Th17 and Th1/17 cells, from healthy donors (HD) and multiple sclerosis (MS) patients and we measured AICD. We find that human Th1 cells are sensitive, whereas ...
Nitrophenyl (NP)-specific helper cells and suppressor cells were induced in vitro using NP-T4 bacteriophage as antigen. These cells could mediate their effects also by secreted effector molecules, helper and suppressor factors. The function of both NP-specific helper and suppressor cells was abolished by treatment with anti-Thy1.2 plus C, but they were not retained on nylon wool columns, suggesting that NP-specific helpers and suppressors were T cells. The membrane phenotype of both NP-specific helper and suppressor cells was found to be Ly1+2+I-J+(I-A-). The secreted effector molecules, helper and suppressor factors which mediate helper or suppressor function, bound to NP immunoadsorbents and are NP-specific in their function. They do not have conventional Ig determinants, but both bear determinants coded by the I-J subregion of H-2. The unusual phenotype of NP-specific helper and suppressor cells is discussed, as is the potential use of these hapten-specific T cells and their secreted effector
Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and