Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production.

Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production.
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DOI:
10.1084/jem.20121932
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发表时间:
2013-01-14
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Pantaleo G
Pantaleo G
中科院分区:
其他
文献类型:
--
作者:
Perreau M;Savoye AL;De Crignis E;Corpataux JM;Cubas R;Haddad EK;De Leval L;Graziosi C;Pantaleo G

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滤泡性T辅助细胞是HIV感染的主要储存库,并在慢性HIV感染期间积累。在本研究中,我们研究了HIV特异性和HIV感染的CD 4 T细胞在不同人群的记忆CD 4 T细胞的分布,这些细胞是从病毒血症HIV感染受试者的淋巴结中分离出来的。根据CXCR 5、PD-1和Bcl-6的表达,鉴定了四种记忆性CD 4 T细胞群:CXCR 5 −PD-1−Bcl-6−、CXCR 5 +PD-1−Bcl-6 −、CXCR 5 −PD-1+Bcl-6−和CXCR 5 +PD-1+Bcl-6+。基于Bcl-6表达和功能特性(IL-21产生和B细胞帮助),认为CXCR 5 +PD-1+Bcl-6+细胞群对应于T滤泡辅助(Tfh)细胞群。我们发现Tfh和CXCR 5 −PD-1+细胞群富含HIV特异性CD 4 T细胞,与健康受试者相比,这些细胞群在病毒血症HIV感染受试者中显著增加。Tfh细胞群含有最高百分比的携带HIV DNA的CD 4 T细胞,并且在支持体外生产性感染方面最有效。在非进行性感染和低病毒血症(<1,000 HIV RNA拷贝)的受试者中,也容易从Tfh细胞中分离出具有复制能力的HIV。然而,只有Tfh细胞的百分比与血浆病毒血症水平相关。这些结果表明,Tfh细胞作为HIV感染、复制和产生的主要CD 4 T细胞区室。
Follicular T helper cells are the major reservoir for HIV infection and accumulate during chronic HIV infection. 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.
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