免疫生物学课件四.pptVIP

树突状细胞的成熟与Th1和Th2细胞的分化的调节机制 中国科学院上海生命科学院 上海巴斯德研究所 孙兵教授(Sun Bing, MD, Ph.D) 电话 E-mail:bsun@sibs.ac.cn The Dendritic Cells 1. Background 1985, Carvalho EM et al., reported that the Leishmania major infect only macrophages in the host and the development of host cell-mediated immunity underlies successful control of the infection. Resistance: DTH (+), produce IFN-g. Susceptibility: DTH(-), produce IL-10 and IL-4. 1991, Heinel FP, et al , established an animal model of Leishmania major infection in C57BL/6 and BALB/c mice. inoculation of L.major into footpad. Resistant C57BL/6 mice, DTH(+), IFN-g mRNA(+), block by anti-IFN-g antibody. Susceptible BALB/c mice, IL-4 and IL-10 mRNA, block byanti-IL-4 antibody 2. Th1 and Th2 subsets 1989, Mosmann,TR and Coffman ,RL described a functional and phenotypic dichotomy among long-term antigen specific, murine CD4+ T helper clones. Th1 clones produced high levels of IFN-g, Lymphotoxin , and IL-2, and mediated DTH and IgG2a isotype switching. Th2 clones produced high levels of IL-4, IL-5, IL-6, and IL-10 and promoted B cell growth and differentiation , eosinophil and mast cell growth and activation, and IgG1 and IgE isotype switching. The action of each subset tended to inhibit the function of the other. 第三节：Th1/Th2细胞的主要特征1. Th1细胞介导细胞免疫 主要的分子标志: Cytokines secretion: IFN-g/CD4+, TNF-a, IL-2 Receptor: IL-12b2, CCR5和CXCR3在 Th1细胞表面。 主要的信号转导分子:STAT4, T-bet, Hlx 主要的功能:介导细胞免疫反应 Th1分化过程中的调节分子及信号转导 Annu. Rev. Immunol. 2003. 21:713–58 2. Th2细胞介导细胞免疫 主要的分子标志： Cytokines secretion: IL-4/CD4+, IL-5 and IL-13 Receptor: CCR3, CCR4, CCR8在 Th2细胞表面 主要的信号转导分子：STAT6, c-maf, GATA3 主要的功能:体液免疫 Th2分化过程中的调节分子及信号转导 Immunological Reviews 2004 Vol. 202: 203–222 Differentiation of CD4+ T cell lineages Helper T cell differentiation and regulation IL-17 cytokine family Treg and Th17 STAT-3 is probably involved in TH17 differentiation, but other TH17-lineage-specific factors may well emerge TGF-β promotes Th17 differentiation Test