J Exp Med：Tfh细胞为HIV病毒在人体内的主要储存库

12月17日在线发表在实验医学杂志（The Journal of Experimental Medicine）的一项研究报告指出，特定的CD4T细胞群是HIV患者体内HIV病毒的主要储存库，也是HIV复制和产生的主要位点。该试验由洛桑大学医院，瑞士疫苗研究所免疫和变态反应部门的Giuseppe Pantaleo教授及Matthieu Perreau博士带领完成。

众所周知，CD4T细胞是HIV的主要靶细胞。其中，这种作为HIV感染的主要存储库及HIV复制和产生的主要位点的CD4T细胞群不存在于血液中，而仅存在于淋巴组织中，这个区域被称之为生发中心。这些CD4T细胞被称为“滤泡辅助性T细胞（Tfh）”，占CD4T细胞总数的2%，存在于淋巴组织中，与B细胞紧密相联，促进B细胞成熟并产生抗体。

Pantaleo博士说：“我们最终确定了这种CD4T细胞群是活性HIV复制和产生的主要原因，也证实了Tfh细胞是患者经逆转录病毒有效治疗后，体内残余病毒复制的主要原因。这是HIV领域的一项重大发现。”

Perreau说：“CD8T细胞一般不会存在于生发中心，而HIV感染的Tfh细胞隐藏于HIV特异性细胞毒性CD8T细胞无法到达生发中心位置。因此，生发中心成为Tfh细胞HIV病毒复制的避难所。”

Pantaleo说：“识别作为HIV主要储存库的CD4T细胞有助于开发选择性的、针对HIV感染的Tfh细胞的治疗方法，消除HIV感染的Tfh细胞将成为HIV治疗的一个新策略。例如，在不进行抗逆转录病毒治疗也可控制HIV病毒的复制及根除HIV病毒。”

doi: 10.1084/jem.20121932
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Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production

Matthieu Perreau1, Anne-Laure Savoye1, Elisa De Crignis1, Jean-Marc Corpataux2, Rafael Cubas5, Elias K. Haddad5, Laurence De Leval3, Cecilia Graziosi1, and Giuseppe Pantaleo1,4

In the present study, we have investigated the distribution of HIV-specific and HIV-infected CD4 T cells within different populations of memory CD4 T cells isolated from lymph nodes of viremic HIV-infected subjects. Four memory CD4 T cell populations were identified on the basis of the expression of CXCR5, PD-1, and Bcl-6: CXCR5−PD-1−Bcl-6−, CXCR5+PD-1−Bcl-6−, CXCR5−PD-1+Bcl-6−, and CXCR5+PD-1+Bcl-6+. On the basis of Bcl-6 expression and functional properties (IL-21 production and B cell help), the CXCR5+PD-1+Bcl-6+ cell population was considered to correspond to the T follicular helper (Tfh) cell population. We show that Tfh and CXCR5−PD-1+ cell populations are enriched in HIV-specific CD4 T cells, and these populations are significantly increased in viremic HIV-infected subjects as compared with healthy subjects. The Tfh cell population contained the highest percentage of CD4 T cells harboring HIV DNA and was the most efficient in supporting productive infection in vitro. Replication competent HIV was also readily isolated from Tfh cells in subjects with nonprogressive infection and low viremia (<1,000 HIV RNA copies). However, only the percentage of Tfh cells correlated with the levels of plasma viremia. These results demonstrate that Tfh cells serve as the major CD4 T cell compartment for HIV infection, replication, and production.