CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
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DOI：
10.1038/s41385-019-0180-2
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发表时间：
2019-09-01
影响因子：
8
通讯作者：
Frater, John
中科院分区：
文献类型：
--
作者：
Thornhill, John P.;Pace, Matthew;Frater, John
肠道相关淋巴组织（GALT）是HIV病毒库的关键位置。观察到b细胞- t细胞双联体在外周血中富含CD32a（一种低亲和力的IgG受体），提出了有趣的问题，特别是在一些研究中这些细胞与HIV DNA有关。我们试图确定是否在GALT中存在类似的双链，这些双链的意义，以及它们对HIV病毒库的影响。鉴于GALT作为HIV储存库的重要性，我们寻找CD32在肠道CD4 T细胞上的表达，寻找双链的证据，以及在原发性HIV感染（PHI）期间开始抗逆转录病毒治疗（ART）的HIV +个体中与HIV DNA的任何关系。扁桃体组织也可用于一个人。如前所述，在血液中，CD32（高）CD4细胞主要是CD4 T细胞和B细胞的双偶体，扁桃体和肠道组织中的T细胞表达ICOS。与CD32相关的CD4 T细胞（与CD32- CD4细胞相比）具有更高的滤泡标记物CXCR5、PD1、ICOS和Bcl-6的表达，与T滤泡辅助细胞（TFH）表型一致。直肠HIV DNA水平与TFH细胞上CD32的表达有显著相关性。总之，这些数据表明CD32（高）双偶体主要由TFH细胞组成，这是一个已知易被HIV感染的亚群。
Gut-associated lymphoid tissue (GALT) is a key location for the HIV reservoir. The observation that B-cell-T-cell doublets are enriched for CD32a (a low-affinity IgG receptor) in peripheral blood raises interesting questions, especially as these cells have been associated with HIV DNA in some studies. We sought to determine if similar doublets were present in GALT, the significance of these doublets, and their implications for the HIV reservoir. Given the importance of GALT as a reservoir for HIV, we looked for expression of CD32 on gut CD4 T cells and for evidence of doublets, and any relationship with HIV DNA in HIV + individuals initiated on antiretroviral therapy (ART) during primary HIV infection (PHI). Tonsil tissue was also available for one individual. As previously shown for blood, CD32(high) CD4 cells were mainly doublets of CD4 T cells and B cells, with T-cell expression of ICOS in tonsil and gut tissue. CD4 T cells associated with CD32 (compared with 'CD32-' CD4 cells) had higher expression of follicular markers CXCR5, PD1, ICOS, and Bcl-6 consistent with a T follicular helper (TFH) phenotype. There was a significant correlation between rectal HIV DNA levels and CD32 expression on TFH cells. Together, these data suggest that CD32(high) doublets are primarily composed of TFH cells, a subset known to be preferentially infected by HIV.