The frequency of α₄β₇(high) memory CD4⁺ T cells correlates with susceptibility to rectal simian immunodeficiency virus infection.
The frequency of α₄β₇(high) memory CD4⁺ T cells correlates with susceptibility to rectal simian immunodeficiency virus infection.
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DOI：
10.1097/qai.0b013e31829f6e1a
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发表时间：
2013-12-01
期刊：
影响因子：
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通讯作者：
Robbiani M
中科院分区：
文献类型：
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作者：
Martinelli E;Veglia F;Goode D;Guerra-Perez N;Aravantinou M;Arthos J;Piatak M Jr;Lifson JD;Blanchard J;Gettie A;Robbiani M
整合素 α4β7 (α4β7) 介导 CD4+ T 细胞归巢至肠道相关淋巴组织 (GALT)，这为 HIV 扩张和传播构成了非常有利的环境。 HIV 和 SIV 包膜蛋白与 α4β7 结合并通过其发出信号，在急性感染期间，SIV 优先感染 α4β7high CD4+ T 细胞。我们假设攻击时这些细胞的可用性可能会影响粘膜 SIV 传播和急性病毒载量 (VL)。我们用 3000 TCID50 的 SIVmac239 直肠攻击 17 只恒河猴，并在攻击前后通过流式细胞术跟踪血液和组织中的 α4β7+ T 和树突状细胞 (DC) 亚群。我们发现，攻击前血液中表达高水平 α4β7（α4β7 高记忆 CD4+ T 细胞）的记忆 CD4+ T 细胞的频率与感染和急性 VL 的易感性密切相关。值得注意的是，不仅在攻击时，攻击前 3 周的频率也与感染相关。这种关联扩展到直肠组织，因为我们观察到攻击前后血液和直肠中α4β7高记忆CD4+ T细胞的频率之间存在很强的直接相关性。 α4β7+髓系DC和α4β7high CD80+DC的频率也与感染和急性VL相关，而血液CCR5+和CD69+CD4+T细胞与感染无关。我们的结果表明，循环系统和直肠组织中 α4β7high CD4+ T 细胞频率较高的动物可能更容易受到 SIV 直肠传播的影响。
Integrin α4β7 (α4β7) mediates the homing of CD4+ T cells to gut-associated lymphoid tissues (GALT), which constitute a highly favorable environment for HIV expansion and dissemination. HIV and SIV envelope proteins bind to and signal through α4β7 and during acute infection SIV preferentially infects α4β7high CD4+ T cells. We postulated that the availability of these cells at the time of challenge could influence mucosal SIV transmission and acute viral load (VL). We challenged 17 rhesus macaques with 3000 TCID50 of SIVmac239 rectally and followed the subsets of α4β7+ T and dendritic cells (DCs) by flow cytometry in blood and tissues, before and after challenge. We found that the frequency of memory CD4+ T cells that expressed high levels of α4β7 (α4β7high memory CD4+ T cells) in blood before challenge correlated strongly with susceptibility to infection and acute VL. Notably, not only at the time of challenge, but also their frequency 3 weeks before challenge correlated with infection. This association extended to the rectal tissue as we observed a strong direct correlation between the frequency of α4β7high memory CD4+ T cells in blood and rectum before and after challenge. The frequency of α4β7+ myeloid DCs and α4β7high CD80+ DCs also correlated with infection and acute VL, while blood CCR5+ and CD69+ CD4+ T cells could not be associated with infection. Our results suggest that animals with higher frequency of α4β7high CD4+ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.