Early restoration of mucosal CD4 memory CCR5 T cells in the gut of SIV-infected rhesus predicts long term non-progression
Early restoration of mucosal CD4 memory CCR5 T cells in the gut of SIV-infected rhesus predicts long term non-progression
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DOI：
10.1097/qad.0b013e3282f08b32
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发表时间：
2007-11-30
期刊：
影响因子：
3.8
通讯作者：
Marx, Preston A.
中科院分区：
文献类型：
--
作者：
Ling, Binhua;Veazey, Ronald S.;Marx, Preston A.
目的：利用感染 SIVmac 的中国恒河猴 (Ch Rh) 来表征长期无进展 (LTNP) 状态的免疫病理学特征。解决的关键问题是LTNP在急性感染过程中是否经历粘膜CD4 T细胞的早期和快速损失以及它们维持LTNP状态的机制。方法：Ch Rh感染SIVmac239。使用多色流式细胞术分析 SIV 感染期间血液、淋巴结和肠道组织中的 T 淋巴细胞亚群。通过 bDNA 测定监测血浆病毒载量。用抗CD8抗体处理两个LTNP以消除体内CD8细胞。结果：在长达6年的低病毒载量的SIVmac239感染的ChRh中，31%(5/16)是LTNP。 LTNP 和进展者在感染前肠道记忆 CD4/CCR5 T 细胞（靶细胞）水平相似，并且两组靶细胞均出现早期和严重的耗竭。 LTNP 的特点是粘膜靶细胞的逐渐恢复，这在感染后 6 个月时很明显。两种 LTNP 体内 CD8 耗竭诱导了 AIDS，其中一种 LTNP (V542) 在抗 CD8 治疗后，另一种 (AJ07) 在病毒血症短暂峰值后仍保持健康。结论：靶细胞的早期破坏在 LTNP 和进展者中是相同的，并且不能预测临床结果。肠道靶细胞的恢复与长期不进展相关。 CD8 T 细胞可能在维持 LTNP 状态中发挥关键作用。 (C) 2007 年 Wolters Kluwer Health 垂直条 Lippincott Williams & Wilkins。
Objectives: To use SIVmac-infected Chinese-origin rhesus macaques (Ch Rh) to characterize the immunopathology of the long term non-progressor (LTNP) state. The key questions addressed were whether or not LTNP experience an early and rapid loss of mucosal CD4 T cells during the acute infection and the mechanisms by which they maintain the LTNP state.Methods: Ch Rh were infected with SIVmac239. Polychromatic flow cytometry was used to analyze T lymphocyte subsets from blood, lymph nodes and gut tissues during SIV infection. Plasma viral loads were monitored by bDNA assay. Two LTNP were treated with anti-CD8 antibody to deplete CD8 cells in vivo.Results: Thirty-one percent (5/16) of SIVmac239-infected ChRh having low viral loads for as long as 6 years were LTNP. Both LTNP and progressors had similar levels of gut memory CD4/CCR5 T cells (target cells) before infection and there was an early and profound depletion of target cells in both groups. LTNP were distinguished by gradual restoration of mucosal target cells which was evident by 6 months post infection. In vivo CD8 depletion in two LTNP induced AIDS in one LTNP (V542) post anti-CD8 treatment and the other (AJ07) remained healthy after a transient spike in viremia.Conclusions: Early destruction of target cells was equivalent in LTNP and progressors and did not predict clinical outcome. Restoration of target cells in the gut is associated with long term non-progression. CD8 T cells may play a critical role on maintaining the LTNP state. (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.