结核特异性CD8+ Treg细胞表型及其作用机制研究

Identifying the precise immune mechanisms that lead to control of initial Mycobacterium tuberculosis infection and preventing reactivation of latent infection are crucial for combating tuberculosis. CD8+ Tregs play important immunoregulatory roles. But the phenotype and mechanism of CD8+Treg cells are not clear in adult tuberculosis infection. The newest research shows that, after antigen stimulation,CD8+Treg cells mainly through the secretion of the suppressive cytokines IL-10 and TGF-β, and induction of APC disabled to exert an inhibitory effect. Our study also found that, tuberculous antigen can induce CD8+T cells to secrete IL-10. These cells do not secrete IFN-γ, without expression of killer related molecules. We speculate that this cell subset is antigen specific CD8+Treg cells induced by Mycobacterium tuberculosis. And these cells might be involved in regulating the immune response of tuberculosis. In this study, we intends to explore the phenotypic characteristics of local antigen specific CD8+Treg cells during Mycobacterium tuberculosis infection, T cell receptor(TCR) Vβ chain composition, cell division and proliferation and inhibition function. It will provide a theoretical basis for making reasonable tuberculosis immune intervention.strategies and developing novel tuberculosis vaccine.

识别机体控制结核感染的免疫机制及预防潜伏感染的再活化，对于控制结核感染至关重要。调节性CD8+T细胞(CD8+Treg)具有重要的免疫调节功能，但成人结核菌感染过程中，CD8+Treg细胞的表型及作用机制尚不明确。最新研究表明，CD8+Treg细胞经抗原刺激后，主要通过分泌抑制性细胞因子IL-10或TGF-β，以及诱导抗原提呈细胞失能发挥抑制作用。我们研究也发现，结核抗原可诱导CD8+T细胞分泌IL-10，这群细胞不分泌IFN-γ，也不表达杀伤相关分子，我们推测这群细胞是结核菌诱导的抗原特异性CD8+Treg细胞，这群细胞很可能参与结核免疫应答的调节。本课题拟探索结核菌感染局部抗原特异性CD8+Treg细胞的表型特征、T细胞受体(TCR) Vβ链组成、细胞分裂和增殖及其抑制功能，为制定合理的结核免疫干预策略以及新型结核疫苗的研发提供理论依据。