*Center for Biomedical Research, Population Council, New York, NY; †Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; ‡AIDS and Cancer Virus Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD; §Tulane National Primate Research Center, Tulane University Sciences Center, Covington, LA; and ‖Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY.
J Acquir Immune Defic Syndr. 2013 Dec 1;64(4):325-31. doi: 10.1097/QAI.0b013e31829f6e1a.
Integrin α₄β₇(high) (α₄β₇(high)) mediates the homing of CD4⁺ T cells to gut-associated lymphoid tissues, which constitute a highly favorable environment for HIV expansion and dissemination. HIV and simian immunodeficiency virus (SIV) envelope proteins bind to and signal through α₄β₇(high) and during acute infection SIV preferentially infects α₄β₇(high) 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(high) T cells 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(high) (α₄β₇(high) 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 α₄β₇(high) memory CD4⁺ T cells in blood and rectum before and after challenge. The frequency of α4β7 myeloid DCs and α₄β₇(high) CD80⁺ DCs also correlated with infection and acute VL, whereas blood CCR5⁺ and CD69⁺ CD4⁺ T cells could not be associated with infection.
Our results suggest that animals with higher frequency of α₄β₇(high) CD4⁺ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.
整合素 α₄β₇(高)（α₄β₇(高)）介导 CD4⁺ T 细胞归巢到肠道相关淋巴组织，这些组织构成了 HIV 扩增和传播的极为有利的环境。HIV 和猴免疫缺陷病毒（SIV）包膜蛋白与 α₄β₇(高)结合并通过其发出信号，在急性感染期间，SIV 优先感染 α₄β₇(高) CD4⁺ T 细胞。我们推测，在挑战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）。
我们通过流式细胞术在血液和组织中检测挑战前后 α₄β₇(高) T 细胞和树突状细胞（DC）的亚群，用 3000 TCID50 的 SIVmac239 通过直肠挑战 17 只恒河猴。
我们发现，挑战前血液中高表达 α₄β₇(高)（α₄β₇(高)记忆 CD4⁺ T 细胞）的记忆 CD4⁺ T 细胞的频率与易感性感染和急性 VL 密切相关。值得注意的是，不仅在挑战时，而且在挑战前 3 周时，它们的频率也与感染相关。这种关联扩展到直肠组织，因为我们观察到在挑战前后血液和直肠中 α₄β₇(高)记忆 CD4⁺ T 细胞的频率之间存在很强的直接相关性。α4β7 髓样 DC 和 α₄β₇(高) CD80⁺ DC 的频率也与感染和急性 VL 相关，而血液中的 CCR5⁺和 CD69⁺ CD4⁺ T 细胞不能与感染相关。
我们的结果表明，循环和直肠组织中 α₄β₇(高) 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。
