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        A human mutant CD4 molecule resistant to HIV-1 bindingrestores helper T-lymphocyte functions in murineCD4-deficient mice

        김동구,Tahara-Hanaoka Satoko,Nobutsuna Shinohara,Hiromitsu Nakauchi 생화학분자생물학회 2007 Experimental and molecular medicine Vol.39 No.1

        CD4 is a cell surface glycoprotein that acts as a co-receptor for the T cell antigen receptor by binding to a non-polymorphic portio n of MHC molecules. CD4 also functions as a receptor for human immuno-deficiency virus type-I (HIV-1) because the viral envelope glycoprotein gp120 binds to CD4 with a high affinity. We have previously demonstrated that introduction of mutations into CD4 abolished the binding of gp120 and prevented HIV-1 from entering cells and spreading. How ever, whether introduction binding to MHC and loss of function is yet to be determined. We generated transgenic mouse lines by injecting a mutant human CD4 (muthCD4) gene under a murine CD4 enhancer/promoter to ensure tissue and stage specific expression. To exclude the influence of endogenous murine CD4, transgenic mice were crossed with murine CD4-targeted mice to produce muthCD4 transgenic mice lacking endo-genous CD4 (muthCD4TG/KO mice). In these mice, T lymphocytes expressing muthCD4 expanded and matured in the thymus and were present in the spleen and lymph nodes. They also activated B cells to mount an antibody response to a T-dependent antigen. The results from this study suggest that a human variant of CD4 modified to be resistant to HIV-1 ment in the thymus in vivo , having helper T cell functions. Thus, further characterization of muthCD4 molecules should open the way to new HIV treatment modalities.

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        Regulation of Immune Responses by the Activating and Inhibitory Myeloid-Associate Immunoglobuline-Like Receptors (MAIR) (CD300)

        Shibuya, Akira,Nakahashi-Oda, Chigusa,Tahara-Hanaoka, Satoko The Korean Association of Immunobiologists 2009 Immune Network Vol.9 No.2

        Activating and inhibitory cell surface receptors play important roles in regulation of immune responses. Recent progress has demonstrated that many inhibitory receptors pair with activating, as well as inhibitory, isoforms, both of whose genes are located in small clusters on a chromosome. We and others identified paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptors (MAIR) (CD300). MAIR is a multigene family consisting of nine genes on a small segment of mouse chromosome 11. MAIR family receptors are preferentially expressed on myeloid cells, including macrophages, dendritic cells, granulocytes, and bone-marrow-derived cultured mast cells, and a subset of B cells and regulate activation of these cells. Thus, MAIR plays an important role in innate immunity mediated by myeloid cells.

      • KCI등재

        Regulation of Immune Responses by the Activating and Inhibitory Myeloid-Associate Immunoglobuline-Like Receptors (MAIR) (CD300)

        Akira Shibuya,Chigusa Nakahashi-Oda,Satoko Tahara-Hanaoka 대한면역학회 2009 Immune Network Vol.9 No.2

        Activating and inhibitory cell surface receptors play important roles in regulation of immune responses. Recent progress has demonstrated that many inhibitory receptors pair with activating, as well as inhibitory, isoforms, both of whose genes are located in small clusters on a chromosome. We and others identified paired activating and inhibitory immunoglobulin- like receptors, designated myeloid-associated immunoglobulin-like receptors (MAIR) (CD300). MAIR is a multigene family consisting of nine genes on a small segment of mouse chromosome 11. MAIR family receptors are preferentially expressed on myeloid cells, including macrophages, dendritic cells, granulocytes, and bone-marrow-derived cultured mast cells, and a subset of B cells and regulate activation of these cells. Thus, MAIR plays an important role in innate immunity mediated by myeloid cells. Activating and inhibitory cell surface receptors play important roles in regulation of immune responses. Recent progress has demonstrated that many inhibitory receptors pair with activating, as well as inhibitory, isoforms, both of whose genes are located in small clusters on a chromosome. We and others identified paired activating and inhibitory immunoglobulin- like receptors, designated myeloid-associated immunoglobulin-like receptors (MAIR) (CD300). MAIR is a multigene family consisting of nine genes on a small segment of mouse chromosome 11. MAIR family receptors are preferentially expressed on myeloid cells, including macrophages, dendritic cells, granulocytes, and bone-marrow-derived cultured mast cells, and a subset of B cells and regulate activation of these cells. Thus, MAIR plays an important role in innate immunity mediated by myeloid cells.

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