Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals
Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals
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DOI：
10.3389/fimmu.2018.00144
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发表时间：
2018-02-05
影响因子：
7.3
通讯作者：
Perreau, Matthieu
中科院分区：
文献类型：
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作者：
Banga, Riddhima;Procopio, Francesco A.;Perreau, Matthieu
我们最近证明，抗逆转录病毒治疗（ART）治疗的HIV感染者的淋巴结（LN）PD-1（+）/T滤泡辅助（Tfh）细胞富含含有复制能力病毒的细胞。然而，含有可诱导复制能力病毒的细胞的分布仅在血液记忆CD 4 T细胞群中部分阐明，包括血液中循环的Tfh细胞对应物（cTfh）。在这种情况下，我们研究了（1）总的HIV感染细胞和（2）含有复制能力和感染性病毒的细胞在常规抗逆转录病毒治疗（cART）治疗的HIV感染个体的各种血液和LN记忆CD 4 T细胞群中的分布。在本研究中，我们表明，血液CXCR 3表达记忆CD 4 T细胞富集在细胞中含有可诱导的复制能力的病毒，并贡献了最多的总池的细胞中含有复制能力和感染性病毒的血液。有趣的是，随后的前病毒序列分析没有表明血液和LN CD 4 T细胞群之间的病毒区室化，表明两个区室之间的动态互换。然后，我们研究了血液HIV储库的组成是否可以反映储库接种时LN CD 4 T细胞的极化，并显示病毒血症未治疗的HIV感染个体的LN PD-1（+）CD 4 T细胞表达的CXCR 3水平显著高于CCR 4和/或CCR 6，表明血液表达CXCR 3的CD 4 T细胞可能来源于LN PD-1（+）CD 4 T细胞。综上所述，这些结果表明，血液CXCR 3表达的CD 4 T细胞代表了治疗的病毒血症HIV感染个体中含有可诱导复制能力病毒的主要血液区室。
We recently demonstrated that lymph nodes (LNs) PD-1(+)/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investigated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1(+) CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1(+) CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment containing inducible replication competent virus in treated aviremic HIV-infected individuals.