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T lymphocytes and cellular immunity Development of T cells T cell surface markers Functions and subset of T cell Activation of T cells What is T cell Thymus-derived lymphocyte: T cell Function1: mediate cellular immunity Function2:immunoregulation Origin:bone marrow stem cell Distributing: T –Zone of secondary lymph node and peripheral blood (65-75% of total lymphocytes) Development of T cell Role of the Thymus in T Cell Maturation The thymus is the major site of maturation of T cells. If the thymus is removed from a neonatal mouse, this animal fails to develop mature T cells. The congenital absence of the thymus, as occurs in the DiGeorge syndrome in humans or in the nude mouse strain, is characterized by low numbers of mature T cells in the circulation and peripheral lymphoid tissues and severe deficiencies in T cell-mediated immunity. Maturation of T cells in the thymus Factors promoting T cell development in the thymus Interaction of cell adhesion molecules between immature thymocytes and thymic stroma cells Cytokines (IL-1, IL-6, IL-7) and hormones secreted by thymic stroma cells Cytokines (IL-2, IL-4) secreted by thymocytes themselves MHC-autoantigen complex on the thymic stroma cells Three Phases Double negative(DN) Double positive (DP) Single positive (SP) Sequential development of thymocytes Pro-T cells CD4-CD8- double-negative thymocytes The majority (90%) of the DN thymocytes will ultimately give rise to αβ TCR-expressing, MHC-restricted CD4+ and CD8+ T cells. RAG-1 and RAG-2 proteins are first expressed at this stage, and Dβ-to-Jβ rearrangements occur first. Sequential development of thymocytes Pre-T cells CD4-CD8- double-negative thymocytes Vβ-to-DJβ rearrangements occur at this stage. The β chain protein is expressed on the cell surface in association with an invariant protein called pre-Tα and with CD3 and ζ proteins to form the pre-T cell receptor (pre-TCR). Pre-T cell receptor The pre-T cell receptor is compose
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