干细胞样记忆型T细胞在HIV-1感染者免疫重建中的作用

Stem cell like memory T cell (Tscm) is thought to be the least differentiated and long-lasting memory T cell subset. The role of Tscm in immune reconstitution in HIV-1 infected patients remains unknown. Our previous studies demonstrated that the differentiation of Tscm lead to a shift in the proportion of T cell subsets could be a possible mechanism to re-establish the homeostasis of the immune system. Therefore, the hypothesis in this proposal is that Tscm may responsible for the immune reconstitution in HIV-1 infected patients. Immunological responders and immunological nonresponders will be recruited in this research. The quantity of Tscm and the capacity of cell differentiation, proliferation and homeostasis of Tscm in these two groups will be analyzed to identify the correlation between the quantity and function of Tscm and immune reconstitution. To determine the correlation between the latent reservoir in Tscm and immune reconstitution, the size of HIV-1 latent reservoir in Tscm in these two groups will be quantified, and the similarity of HIV-1 env gene, subtype, and coreceptor usage of provirus in Tscm will also be analyzed. This study will contribute to the further understanding of the role of Tscm in immune reconstitution, and also identify a potential target for the HIV-1 immune therapy and vaccine development.

干细胞样记忆型T细胞（Tscm）是最早期分化的、存在时间最长的记忆型T细胞。Tscm在HIV-1患者免疫重建中的作用尚不清楚。我们前期研究发现，Tscm分化引起T细胞亚群间比例的变化有可能是免疫系统稳态重建的机制之一。因此，本课题的假说为Tscm的数量、功能及Tscm中病毒储藏库大小会影响HIV-1患者免疫功能重建。为此，我们拟入组HIV-1免疫应答者和免疫不应答者，通过对两组患者Tscm数量、分化能力、增殖能力和稳态的分析，了解Tscm数量和功能与免疫重建的相关性；通过对这两组患者Tscm中HIV-1病毒储藏库的大小进行定量并分析潜伏HIV-1 env序列、病毒亚型及辅受体使用，了解Tscm中病毒储藏库对免疫重建的影响。该研究将有助于深入探讨Tscm细胞在HIV-1患者免疫重建中的作用，同时也为HIV-1治疗及疫苗开发提供新的思路和前景。

干细胞样记忆型T细胞（Tscm）是最早期分化的、存在时间最长的记忆型T细胞。Tscm在HIV-1患者免疫重建中的作用尚不清楚。本项目中，我们对HIV-1感染者抗病毒治疗前后Tscm的比例、数量、增殖水平、活化水平及其储藏库进行了研究，结果发现基线Tscm与HIV-1疾病进展相关，影响ART后CD4+T细胞的恢复，机制研究表明，ART后Tscm的增殖水平影响免疫重建效果。此外，活化的Tscm通过上调其表面TIGIT分子抑制T细胞功能。此项目初步阐明Tscm影响免疫重建的机制，并提示我们密切观察Tscm的活化水平对于T细胞功能恢复有着重要的意义。此项研究说明深入研究Tscm的功能特点将有助于开发新的HIV-1免疫疗法。