12月17日在線發表在實驗醫學雜誌(The Journal of Experimental Medicine)的一項研究報告指出,特定的CD4T細胞群是HIV患者體內HIV病毒的主要儲存庫,也是HIV複製和產生的主要位點。該試驗由洛桑大學醫院,瑞士疫苗研究所免疫和變態反應部門的Giuseppe Pantaleo教授及Matthieu Perreau博士帶領完成。
眾所周知,CD4T細胞是HIV的主要靶細胞。其中,這種作為HIV感染的主要存儲庫及HIV複製和產生的主要位點的CD4T細胞群不存在於血液中,而僅存在於淋巴組織中,這個區域被稱之為生發中心。這些CD4T細胞被稱為「濾泡輔助性T細胞(Tfh)」,佔CD4T細胞總數的2%,存在於淋巴組織中,與B細胞緊密相聯,促進B細胞成熟並產生抗體。
Pantaleo博士說:「我們最終確定了這種CD4T細胞群是活性HIV複製和產生的主要原因,也證實了Tfh細胞是患者經逆轉錄病毒有效治療後,體內殘餘病毒複製的主要原因。這是HIV領域的一項重大發現。」
Perreau說:「CD8T細胞一般不會存在於生發中心,而HIV感染的Tfh細胞隱藏於HIV特異性細胞毒性CD8T細胞無法到達生發中心位置。因此,生發中心成為Tfh細胞HIV病毒複製的避難所。」
Pantaleo說:「識別作為HIV主要儲存庫的CD4T細胞有助於開發選擇性的、針對HIV感染的Tfh細胞的治療方法,消除HIV感染的Tfh細胞將成為HIV治療的一個新策略。例如,在不進行抗逆轉錄病毒治療也可控制HIV病毒的複製及根除HIV病毒。」(生物谷Bioon.com)
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.