Integrin α₄β₇ mediates the trafficking of leukocytes, including CD4⁺ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α₄β₇ mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4⁺ cells in rhesus macaques infected with SIV. We determined that α₄β₇ mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes. These sites are not directly linked to α₄β₇ mediated homing; however, the most pronounced reduction in viral load was observed in the colon. Despite this reduction, α₄β₇ mAb treatment did not prevent an apparent depletion of CD4⁺ T cells in gut in the acute phase of infection that is characteristic of HIV/SIV infection. However, α₄β₇ mAb appeared to facilitate the preservation or restoration of CD4⁺ T cells in gut tissues at later stages of infection. Since damage to the gut is believed to play a central role in HIV pathogenesis, these results support further evaluation of α₄β₇ antagonists in the study and treatment of HIV disease.

中文翻译：

---

用 α4β7 mAb 早期治疗 SIV+ 猕猴可改变病毒分布，并在感染后期保留 CD4+ T 细胞。


整合素 α ₄ β ₇介导白细胞（包括 CD4 ⁺ T 细胞）向肠道淋巴组织的运输。病毒介导的肠道损伤与 HIV 和 SIV 介导的慢性免疫激活有关，并导致免疫系统不可逆转的损伤。我们采用免疫 PET/CT 成像技术来评估单独使用抗整合素 α ₄ β ₇ mAb 或与 ART 联合使用对感染 SIV 的恒河猴中 SIV 感染细胞和 CD4 ⁺细胞分布的影响。我们确定 α ₄ β ₇ mAb 可以减少肺、脾、腋窝和腹股沟淋巴结等一系列组织中的病毒抗原。这些位点与 α ₄ β ₇介导的归巢没有直接关系；然而，在结肠中观察到病毒载量最明显的减少。尽管这种减少，α ₄ β ₇ mAb 治疗并不能阻止感染急性期肠道中 CD4 ⁺ T 细胞的明显消耗，这是 HIV/SIV 感染的特征。然而，α ₄ β ₇ mAb 似乎有助于感染后期肠道组织中 CD4 ⁺ T 细胞的保存或恢复。由于肠道损伤被认为在 HIV 发病机制中发挥着核心作用，因此这些结果支持在 HIV 疾病的研究和治疗中进一步评估 α ₄ β ₇拮抗剂。