1993 Fiscal Year Final Research Report Summary
Studies on the pathogenesis of immunological disorders by analysis of the process of differentiation and acquirement of specificity of the lymphocytes.
| Project/Area Number |
03454261
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
YATA Junichi Tokyo Medical and Dental University, School of Medicine Professor, 医学部, 教授 (60057502)
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| Project Period (FY) |
1991 – 1993
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| Keywords | severe combined immunodeficiency / Ig gene / Wiskott-Aldrich syndrome / IL-2 receptor gamma chain / CD8 / IL-4 / allergy / CD40 ligand |
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| Research Abstract |
In order to investigate the process of lymphocyte differentiation, culture cell lines were established from malignant lymphoma. Among these, one cell line showing surface phenotype of pre-T cells displayd proliferative response to IL-4 but not to IL-2, which indicated that the cytokines required to support the growth of the cells are different according to differentiation stages.
X-linked severe combined immunodeficiency is the disease characterized by decrease of T cells and hypogammaglobulinemia and caused by the abnormality of the gene of IL-2 receptor gamma chain. This gamma chain is thought to be associated with receptors of not only IL-2 but also IL-4 which induces proliferation and differentiation of B cells and IL-7 which supports the growth of immature lymphocytes. Therefore, the defect of the gamma chain may affects the differentiation of B cells. To clarify this point, hypervariable region of immunoglobulin H chain gene was analyzed and it was found that the rearrangement of
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genes occurs almost normally, but somatic mutation which is essential for affinity maturation of the antibody was lacking. This result indicated that IL-2 receptor gamma chain is important also for B cell maturation.
Mature T cells are divided into CD4 bearing and CD8 bearing subsets. CD8 molecule is composed of two peptide chains. The appearance of alpha-beta heterodimer type of CD8 is thought dependent on the interaction with MHC class I molecule on thymic stroma cells. Most of the CD8 bearing T cells from primary cellular immunodeficiency such as Wiskott-Aldrich syndrome showed alpha-alpha homodimer type of CD8, which suggested that thymic differentiation of T cells is defective in these patients.13EA04 : IgE production from B cells is promoted by IL-4 and ligand binding to CD40 molecules on B cells and inhibited by interferon gamma. The T cell lines established on stimulation by nominal allergens from allergic patients secreted more IL-4 than non-allergic individuals. It may be related to IgE response to allergens that the T cells of allergic patients are prone to produce IL-4 on stimulation by allergens. Less
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