Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques.,Mucosal Immunology

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Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-11-13 , DOI: 10.1038/s41385-019-0221-x
Henintsoa Rabezanahary ₁ , Félicien Moukambi ₁ , David Palesch ₂ , Julien Clain ₁ , Gina Racine ₁ , Guadalupe Andreani ₁ , Ghita Benmadid-Laktout ₁ , Ouafa Zghidi-Abouzid ₁ , Calayselvy Soundaramourty ₃ , Cécile Tremblay ₄ , Guido Silvestri ₂ , Jérôme Estaquier _{1,

3}

Affiliation

Whereas antiretroviral therapy (ART) suppresses viral replication, ART discontinuation results in viral rebound, indicating the presence of viral reservoirs (VRs) established within lymphoid tissues. Herein, by sorting CD4 T-cell subsets from the spleen, mesenteric and peripheral lymph nodes (LNs) of SIVmac251-infected rhesus macaques (RMs), we demonstrate that effector memory (TEM) and follicular helper (TFH) CD4+ T cells harbor the highest frequency of viral DNA and RNA, as well of early R-U5 transcripts in ART-naïve RMs. Furthermore, our results highlight that these two CD4 T cells subsets harbor viral DNA and early R-U5 transcripts in the spleen and mesenteric LNs (but not in peripheral LN) of RMs treated with ART at day 4 post infection suggesting that these two anatomical sites are important for viral persistence. Finally, after ART interruption, we demonstrate the rapid and, compared to peripheral LNs, earlier seeding of SIV in spleen and mesenteric LNs, thereby emphasizing the importance of these two anatomical sites for viral replication dynamics. Altogether our results advance understanding of early viral seeding in which visceral lymphoid tissues are crucial in maintaining TEM and TFH VRs.

中文翻译：

尽管早期抗逆转录病毒治疗效应记忆和滤泡辅助 CD4 T 细胞是 SIV 感染的猕猴内脏淋巴组织的主要储库。

抗逆转录病毒疗法 (ART) 抑制病毒复制，而停用 ART 会导致病毒反弹，表明在淋巴组织内建立了病毒库 (VR)。在此，通过对 SIVmac251 感染的恒河猴 (RM) 的脾脏、肠系膜和外周淋巴结 (LN) 中的 CD4 T 细胞亚群进行分类，我们证明效应记忆 (TEM) 和滤泡辅助 (TFH) CD4+ T 细胞具有病毒 DNA 和 RNA 的最高频率，以及 ART 幼稚 RM 中的早期 R-U5 转录本。此外，我们的结果强调，这两个 CD4 T 细胞亚群在感染后第 4 天接受 ART 治疗的 RM 的脾脏和肠系膜 LN（但不在外周 LN）中含有病毒 DNA 和早期 R-U5 转录本，表明这两个解剖部位对病毒的持久性很重要。最后，在 ART 中断后，我们证明了 SIV 在脾脏和肠系膜 LN 中的快速播种，并且与外周 LN 相比，更早播种，从而强调了这两个解剖部位对病毒复制动力学的重要性。总之，我们的结果促进了对早期病毒播种的理解，其中内脏淋巴组织对于维持 TEM 和 TFH VR 至关重要。

更新日期：2019-11-14

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