Resistance of CD7-deficient mice to lipopolysaccharide-induced shock syndromes.
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CD7 is an immunoglobulin superfamily molecule involved in T and natural killer (NK) cell activation and cytokine production. CD7-deficient animals develop normally but have antigen-specific defects in interferon (IFN)-gamma production and CD8(+) CTL generation. To determine the in vivo role of CD7 in systems dependent on IFN-gamma, the response of CD7-deficient mice to lipopolysaccharide (LPS)-induced shock syndromes was studied. In the high-dose LPS-induced shock model, 67% of CD7-deficient mice survived LPS injection, whereas 19% of control C57BL/6 mice survived LPS challenge (P < 0.001). CD7-deficient or C57BL/6 control mice were next injected with low-dose LPS (1 microgram plus 8 mg D-galactosamine [D-gal] per mouse) and monitored for survival. All CD7-deficient mice were alive 72 h after injection of LPS compared with 20% of C57BL/6 control mice (P < 0.001). After injection of LPS and D-gal, CD7-deficient mice had decreased serum IFN-gamma and tumor necrosis factor (TNF)-alpha levels compared with control C57BL/6 mice (P < 0.001). Steady-state mRNA levels for IFN-gamma and TNF-alpha in liver tissue were also significantly decreased in CD7-deficient mice compared with controls (P < 0.05). In contrast, CD7-deficient animals had normal liver interleukin (IL)-12, IL-18, and interleukin 1 converting enzyme (ICE) mRNA levels, and CD7-deficient splenocytes had normal IFN-gamma responses when stimulated with IL-12 and IL-18 in vitro. NK1.1(+)/ CD3(+) T cells are known to be key effector cells in the pathogenesis of toxic shock. Phenotypic analysis of liver mononuclear cells revealed that CD7-deficient mice had fewer numbers of liver NK1.1(+)/CD3(+) T cells (1.5 +/- 0.3 x 10(5)) versus C57BL/6 control mice (3.7 +/- 0.8 x 10(5); P < 0.05), whereas numbers of liver NK1.1(+)/CD3(-) NK cells were not different from controls. Thus, targeted disruption of CD7 leads to a selective deficiency of liver NK1.1(+)/ CD3(+) T cells, and is associated with resistance to LPS shock. These data suggest that CD7 is a key molecule in the inflammatory response leading to LPS-induced shock. (+info)
Reduced IL-4 and interferon-gamma (IFN-gamma) expression by CD4 T cells in patients with chronic lymphocytic leukaemia.
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CD7 co-expression by CD4 T cells has been reported to be higher in the Th1 compared with the Th2 functional subset. Clinical immunodeficiency and immune dysregulation are more prevalent in the advanced stages of B cell chronic lymphocytic leukaemia (B-CLL). To analyse this further 25 patients with B-CLL and 11 healthy subjects were examined for cell surface CD7 and intracellular IFN-gamma and IL-4 expression in the peripheral blood CD4+ T helper cell population. Significantly decreased CD7, IFN-gamma and IL-4 expression was observed in the patients with B-CLL (P < 0.001). While CD7 negativity and IL-4 expression were more frequent in the later stages of the disease, this did not attain statistical significance. These results suggest a possible explanation for the reduced cellular and humoral immunity in B-CLL. (+info)
CD56+CD7+ stem cell leukemia/lymphoma with D2-Jdelta1 rearrangement.
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OBJECT: We describe the characteristics of three patients with CD56+CD7+ stem cell leukemia/lymphoma. METHODS: These blasts were analyzed for morphologic, karyotypic, immunophenotypic, and immunogenotypic features using Southern blot and polymerase chain reaction analysis. MATERIALS: Peripheral blood, bone marrow aspirates, or biopsied mediastinal tumor specimens of three CD56+CD7+ stem cell leukemia/lymphoma patients were investigated. RESULTS: The bone marrow of all patients showed myeloperoxidase (MPO) negative blast cells with basophilic cytoplasm and distinct nucleoli with no azurophilic granules. The blasts of two patients were classified as acute lymphoblastic leukemia (L2). The liver, spleen, and lymph nodes were unaffected in all patients. All had an aggressive clinical course. The blasts were strongly positive for both CD7 and CD56 but negative for other T-lineage associated antigens, including CD1, CD2, surface membrane CD3, cytoplasmic CD3c (2/2), CD4, CD5 and CD8. The additional antigens were recognized as follows: CD19 (1/3 cases) as a B lineage, CD33 (1/3) as a myeloid marker, CD34 (2/3) as a stem cell, CD38 (1/1) and HLA-DR (2/3). When the patients relapsed, the phenotypes changed to blasts positive for CD5, CD10 and CD13 in patient 1, CD5 in patient 2, and CD33 in patient 3. MPO, however, remained negative. Cytogenetic analysis showed no common abnormal karyotype. All had a common D2-Jdelta1 induced by T-cell specific enhancer. Rearrangement of TCR beta and gamma genes occurred in patient 2, and IgH and TCR beta underwent rearrangement in patient 3. CONCLUSION: Although a more comprehensive case analysis is necessary, these data suggest the possibility that the blasts of the present cases come from a common lymphoid precursor (T, NK, and B cell) or from a NKT precursor as the fourth lymphoid lineage. (+info)
Flow cytometric immunophenotyping in fine-needle aspiration of lymph nodes.
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Fine-needle aspiration (FNA) of lymph nodes has been regarded as a useful method in the diagnosis of lymphadenopathy. However, this procedure has been shown to be of limited value in the diagnosis of low or intermediate grade malignant lymphomas in some studies. Immunophenotyping is an essential adjunct to cytomorphology for the diagnosis of lymphoma by FNA. Immunophenotyping using flow cytometry (FCM) is rapid, objective and reliable. Using FCM, multiparametric analysis of 33 FNA materials from lymph nodes was performed and profiles of surface markers of lymphoid cells were assessed. In reactive hyperplasia, patterns of cell surface markers were quite variable, but disclosed polyclonality. Most of the B-cell lymphomas showed immunophenotypes for B-cell lineages with their kappa: lambda or lambda: kappa ratio being over 3:1. In T-cell lymphomas, T-cell surface markers were predominantly expressed as well. In conclusion, our results suggest that immunophenotyping of lymph node aspirates is a valuable diagnostic adjunct for lymphoproliferative disorders, particularly in B-cell lymphomas because immunophenotyping can be easily and adequately performed by FCM. (+info)
Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1.
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Galectin-1 induces apoptosis of human thymocytes and activated T cells by an unknown mechanism. Apoptosis is a novel function for a mammalian lectin; moreover, given the ubiquitous distribution of the oligosaccharide ligand recognized by galectin-1, it is not clear how susceptibility to and signaling by galectin-1 is regulated. We have determined that galectin-1 binds to a restricted set of T cell surface glycoproteins, and that only CD45, CD43, and CD7 appear to directly participate in galectin-1-induced apoptosis. To determine whether these specific glycoproteins interact cooperatively or independently to deliver the galectin-1 death signal, we examined the cell surface localization of CD45, CD43, CD7, and CD3 after galectin-1 binding to human T cell lines and human thymocytes. We found that galectin-1 binding resulted in a dramatic redistribution of these glycoproteins into segregated membrane microdomains on the cell surface. CD45 and CD3 colocalized on large islands on apoptotic blebs protruding from the cell surface. These islands also included externalized phosphatidylserine. In addition, the exposure of phosphatidylserine on the surface of galectin-1-treated cells occurred very rapidly. CD7 and CD43 colocalized in small patches away from the membrane blebs, which excluded externalized phosphatidylserine. Receptor segregation was not seen on cells that did not die in response to galectin-1, including mature thymocytes, suggesting that spatial redistribution of receptors into specific microdomains is required for triggering apoptosis. (+info)
Skewed expression of activation, differentiation and homing-related antigens in circulating cells from patients with cutaneous T cell lymphoma associated with CD7- T helper lymphocytes expansion.
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Mycosis fungoides and Sezary syndrome represent the most frequent forms of cutaneous T cell lymphoma. Both are characterized by skin infiltrating and/or circulating malignant cells displaying a CD4+CD7- phenotype in the majority of cases. Because an expansion of CD4+CD7- cells may also be found in inflammatory dermatoses or in the aging process, we evaluated, by flow cytometry, the relationship between CD7 expression and the distribution of differentiation/activation or homing antigens on peripheral blood lymphocytes from 36 cutaneous T cell lymphoma patients and from healthy donors. CD4+CD7- cells were increased in all patients with cutaneous T cell lymphoma. As a consequence, the CD7+/- ratio was reduced in stage I-II mycosis fungoides (3.96 vs 6.55 in healthy donors), and inverted in stage III-IV MF and Sezary syndrome (0.28 and 0.12 respectively). In the late stage of disease, the CD7+/- inverted ratio was strictly related to the expression of CD15s, CD60, and CD45R0, and the lack of expression of CD26 and CD49d. Interestingly, in leukemic patients, this phenotype was also associated with peculiar morphologic (large size) or phenotypical (CD3dim expression) characteristics. Furthermore, a progressive reduction of circulating CD8+ cells was also seen throughout all stages of disease. The presence of these populations in cutaneous T cell lymphoma at late phases of disease and Sezary syndrome suggests that all of these molecules may play an important part in the activation pathway and skin homing of circulating T cells in lymphoproliferative disorders. Therefore, this may constitute a distinctive feature in cutaneous T cell lymphoma patients with more aggressive characteristics. (+info)
CD4 + /CD7- T cell frequency and polymerase chain reaction-based clonality assay correlate with stage in cutaneous T cell lymphomas.
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In cutaneous T cell lymphomas, tumor cells can be found in skin and in other compartments. A precise definition of extracutaneous spread including blood involvement is necessary for staging and treatment design. We investigated peripheral blood in 51 patients with various types of cutaneous T cell lymphomas by the analysis of blood smears for Sezary cells, the CD4 + /CD7- T helper cell frequency in the peripheral blood by fluorescence activated cell sorter analysis and by polymerase chain reaction for the T cell receptor gamma-chain followed by denaturing gradient gel electrophoresis. Eleven polymerase chain reaction products were sequenced. Thirty-five per cent of patients with stage Ia-IIb cutaneous T cell lymphomas presented a peripheral blood T cell clone. In patients with stage III-IVb cutaneous T cell lymphomas 75% were positive for clonality in the peripheral blood by polymerase chain reaction. Interestingly, three of 13 Sezary patients showed a TCR-gamma joining region pseudogene (JgammaP1/JgammaP2) usage. CD4 + /CD7- cell counts were significantly higher in patients with advanced cutaneous T cell lymphomas than in patients with early cutaneous T cell lymphomas. There was a correlation between increased percentage of circulating CD4 + /CD7- cells and detection of clonality by polymerase chain reaction (p = 0.001). There was no significant correlation between the polymerase chain reaction data and the percentage of Sezary cells on blood smears. A significant correlation between CD4 + /CD7- cells and Sezary cells was found, however. Stepwise logistic regression analysis showed that the CD4 + /CD7- cell count and clonal T cell detection in peripheral blood are independently correlated with stage. The combination of both parameters gives more information than each one separately. In conclusion, our data indicate that fluorescence activated cell sorter analysis of peripheral blood and polymerase chain reaction-based clonality assays can improve the accuracy of staging investigations in cutaneous T cell lymphomas patients. (+info)
Identification of CD7 as a cognate of the human K12 (SECTM1) protein.
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CD7 is a 40-kDa protein found primarily on T, NK, and pre-B cells; the function of the CD7 protein in the immune system is largely unknown. The K12 (SECTM1) protein was originally identified by its location just upstream of the CD7 locus. The K12 gene encodes a transmembrane protein of unknown function. In order to clone a K12-binding protein, we generated a soluble version of the human K12 protein by fusing its extracellular domain to the Fc portion of human IgG(1). Flow cytometry experiments showed that the K12-Fc fusion protein bound at high levels to both human T and NK cells. Precipitation experiments using K12-Fc on (35)S-radiolabeled NK cells lysates indicated that the K12 cognate was an approximately 40-kDa protein. A human peripheral blood T cell cDNA expression library was screened with the K12-Fc protein, and two independent, positive cDNA clones were identified and sequenced. Both cDNAs encoded the same protein, which was CD7. Thus, K12 and CD7 are cognate proteins that are located next to each other on human chromosome 17q25. Additionally, we have cloned the gene encoding the mouse homologue of K12, shown that it maps near the mouse CD7 gene on chromosome 11, and established that the mouse K12 protein binds to mouse, but not human, CD7. Mouse K12-Fc inhibited in a dose-dependent manner concanavalin A-induced proliferation, but not anti-TcRalpha/beta induced proliferation, of mouse lymph node T cells. Human K12-Fc stimulated the up-regulation of CD25, CD54, and CD69 on human NK cells in vitro. (+info)