CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype.,Mucosal Immunology

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CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-06-25 , DOI: 10.1038/s41385-019-0180-2
John P Thornhill _{1,

2} , Matthew Pace ₁ , Genevieve E Martin ₁ , Jonathan Hoare ₂ , Simon Peake ₂ , Carolina Herrera ₂ , Chan Phetsouphanh ₁ , Jodi Meyerowitz ₁ , Emily Hopkins ₁ , Helen Brown ₁ , Polly Dunn ₁ , Natalia Olejniczak ₁ , Christian Willberg _{1,

3} , Paul Klenerman ₁ , Rob Goldin ₂ , Julie Fox ₄ , Sarah Fidler _{2,

5} , John Frater _{1,

6} ,

Affiliation

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, CD32high 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, PD-1, 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 CD32high doublets are primarily composed of TFH cells, a subset known to be preferentially infected by HIV.

中文翻译：

HIV 感染的肠道相关淋巴组织中表达 CD32 的双联体与 T 滤泡辅助细胞表型相关。

肠道相关淋巴组织 (GALT) 是 HIV 储存库的关键位置。B 细胞-T 细胞双联体在外周血中富含 CD32a（一种低亲和力 IgG 受体）的观察结果引发了有趣的问题，特别是因为在一些研究中这些细胞与 HIV DNA 相关。我们试图确定 GALT 中是否存在类似的双联体、这些双联体的重要性及其对 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 细胞上的表达和双联体的证据，以及与 HIV + 个体在原发 HIV 感染期间开始抗逆转录病毒治疗 (ART) 的 HIV DNA 的任何关系（披）。扁桃体组织也可用于一个人。如先前的血液所示，CD32high CD4 细胞主要是 CD4 T 细胞和 B 细胞的双联体，在扁桃体和肠道组织中 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、PD-1、ICOS 和 Bcl-6 表达，与 T 滤泡辅助细胞 (TFH) 表型一致。直肠 HIV DNA 水平与 TFH 细胞上的 CD32 表达之间存在显着相关性。总之，这些数据表明 CD32high 双联体主要由 TFH 细胞组成，TFH 细胞是已知优先感染 HIV 的一个子集。直肠 HIV DNA 水平与 TFH 细胞上的 CD32 表达之间存在显着相关性。总之，这些数据表明 CD32high 双联体主要由 TFH 细胞组成，TFH 细胞是已知优先感染 HIV 的一个子集。直肠 HIV DNA 水平与 TFH 细胞上的 CD32 表达之间存在显着相关性。总之，这些数据表明 CD32high 双联体主要由 TFH 细胞组成，TFH 细胞是已知优先感染 HIV 的一个子集。

更新日期：2019-11-18

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