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1、,T 细胞亚群,何睿 免疫学系 上海医学院 复旦大学,Classes of lymphocytes,T 细胞亚群 T 细胞活化分子机制 T 细胞免疫应答及其效应,自身免疫和超敏反应,T cell subsets, T cells and T cells CD4+T cells and CD8+T Nave T cells（初始T细胞） Effector T cells （效应T细胞） Memory T cells （记忆T细胞） T helper (Th) 辅助性CD4+T细胞 Cytotoxic T cells (CTLs) 细胞毒性CD8+T细胞 Regulatory T cells (
2、Tregs) 调节性CD4+T细胞,T Cell subsets, T cells,express a limited number of TCRs abundant in epithelial tissues of certain species: in the small bowel mucosa and in the skin of mouse. In the skin, known as a dendritic epidermal T cell (DETC) do not recognize MHC-associated peptide antigens and are not MHC
3、 restricted. may bind to conserved ligands whose expression is triggered by cell injury or stress, such as microbial heat shock proteins. may represent an important bridge between innate and adaptive immunity, functioning as lymphocytes that enhance the first line of defense against a range of patho
4、gens.,Jensen, K. D. et al. Thymic selection determines T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon Immunity 29, 90100 (2008).,Epithelial T cell and Peripheral T cell CD27-IL-17+ T cells and CD27+IFN-+ T cells,Subsets of T cells,Developm
5、ental programming of T cell subsets.,Cua DJ, et al. Nature review Immunology, 2010,Martin B et al. IL-17-Producing T cells Selectively Expand in Response to Pathogen Products and Environmental Signals. Immunity 31, 321330 (2009). They show that T-17 cells additionally express IL-23R , and the innate
6、 receptors TLR2 and dectin-1, which recognize archetypical and fungal constituents. These T-17 cells use these receptors to rapidly produce IL-17 in response to bystander cell-derived IL-23 and to bacteria and fungi without concomitant TCR stimulation. One of the roles of T-17-derived may be indirec
7、t or direct amplification of IL-17 production in Th17 cells. Sutton, C. E. et al. Interleukin-1 and IL-23 induce innate IL-17 production from T cells, amplifying Th17 responses and autoimmunity. Immunity 31, 331341 (2009). This report shows that T cells have an early role in promoting CNS inflammati
8、on. The authors suggest that innate cell-produced IL-17 directly enhances development of MOG-specific Th17 cells.,A major innate source of IL-17,Innate Activation of IL-17-Production by a Specialized T Cell Subset,Kapsenberg ML. Immunity,2009,Witherden,et al. The junctional adhesion molecule JAML is
9、 a costimulatory receptor for epithelial T cell activation. Science 2010 Sep Identify an epithelial T cells-specific costimulatory molecule, JAML Petermann F, et al. T cells enhance autoimmunity by restraining regulatory T cells responses via an IL-23-dependeng mechanism. Immunity, 2010 Sep IL-23-ac
10、tivated render effector T cells refractory to the suppressive activity of Treg cells and also prevented the conversion of conventional T cells into Foxp3+Treg cells in vivo.,Two new papers about T Cell published in this month,Nave T cells Mature T cells that have not previously encountered antigen;
11、Preferential migration to secondary lymphoid organs (lymph nodes), where they recognize antigen Effector T cells Activated T cells capable of performing the functions required to eliminate foreign antigens Preferential migration to sites of infection or inflammation Short-lived Memory T cells Long-l
12、ived, functionally silent cells; Mount rapid secondary immune responses to the same antigen exposure Heterogenous (central and effector),Based on the history of antigen encounter and the stage of T cell activation.,Central memory T cells express CCR7 and L-selectin, and home to lymph nodes. limited
13、capacity to perform effector functions when they encounter antigen generate many effector cells upon antigen challenge Effector memory T cells do not express CCR7 or L-selectin, and home to peripheral tissues, especially mucosa. produce effector cytokines upon antigenic stimulation do not proliferat
14、e much.,Based on their homing properties and effector functions.,Subsets of memory T cells,CD4+,CD8+,CD4+,Th1-Th2 hypothesis 1986 Coffman and Mossman Th17 2006,Discovery of CD4+ Th cell subsets,The subsets of CD4+Th cells,How they are induced, What cytokines they produce What effector mechanisms the
15、y activate,Th0,Cytokines,Stimuli that influence the pattern of Th cell differentiation,High doses of antigen without adjuvants Different subsets of dendritic cells may exist The genetic makeup of the host,Properties of CD4+ Th1 and Th2 subsets,Differentiation of Th1 Subset,Stimulated by intracellula
16、r microbes that infect or activate macrophages or NK cells Listeria, mycobacteria and Leishmania,Important cytokines for the Th1 differentiation,Important transcription factors (TF) for the Th1 differentiation,IL-12 IFN- IL-18 type I IFNs (in human),T-bet: master regulator STAT4 STAT1,The molecular basis of Th1 differentiation,The interplay of signals from the T cell receptor, the cyto
