12月17日在線發(fā)表在實(shí)驗(yàn)醫(yī)學(xué)雜志（The Journal of Experimental Medicine）的一項(xiàng)研究報(bào)告指出,，特定的CD4T細(xì)胞群是HIV患者體內(nèi)HIV病毒的主要儲(chǔ)存庫(kù),，也是HIV復(fù)制和產(chǎn)生的主要位點(diǎn)。該試驗(yàn)由洛桑大學(xué)醫(yī)院,，瑞士疫苗研究所免疫和變態(tài)反應(yīng)部門的Giuseppe Pantaleo教授及Matthieu Perreau博士帶領(lǐng)完成,。
眾所周知，CD4T細(xì)胞是HIV的主要靶細(xì)胞,。其中,，這種作為HIV感染的主要存儲(chǔ)庫(kù)及HIV復(fù)制和產(chǎn)生的主要位點(diǎn)的CD4T細(xì)胞群不存在于血液中，而僅存在于淋巴組織中，這個(gè)區(qū)域被稱之為生發(fā)中心,。這些CD4T細(xì)胞被稱為“濾泡輔助性T細(xì)胞（Tfh）”,，占CD4T細(xì)胞總數(shù)的2%，存在于淋巴組織中,，與B細(xì)胞緊密相聯(lián),，促進(jìn)B細(xì)胞成熟并產(chǎn)生抗體。
Pantaleo博士說(shuō)：“我們最終確定了這種CD4T細(xì)胞群是活性HIV復(fù)制和產(chǎn)生的主要原因,，也證實(shí)了Tfh細(xì)胞是患者經(jīng)逆轉(zhuǎn)錄病毒有效治療后,，體內(nèi)殘余病毒復(fù)制的主要原因。這是HIV領(lǐng)域的一項(xiàng)重大發(fā)現(xiàn),。”
Perreau說(shuō)：“CD8T細(xì)胞一般不會(huì)存在于生發(fā)中心,，而HIV感染的Tfh細(xì)胞隱藏于HIV特異性細(xì)胞毒性CD8T細(xì)胞無(wú)法到達(dá)生發(fā)中心位置。因此,，生發(fā)中心成為Tfh細(xì)胞HIV病毒復(fù)制的避難所,。”
Pantaleo說(shuō)：“識(shí)別作為HIV主要儲(chǔ)存庫(kù)的CD4T細(xì)胞有助于開(kāi)發(fā)選擇性的、針對(duì)HIV感染的Tfh細(xì)胞的治療方法,，消除HIV感染的Tfh細(xì)胞將成為HIV治療的一個(gè)新策略,。例如，在不進(jìn)行抗逆轉(zhuǎn)錄病毒治療也可控制HIV病毒的復(fù)制及根除HIV病毒,。”(生物谷Bioon.com)
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.
