Ling Binhua, Veazey Ronald S, Hart Mike, Lackner Andrew A, Kuroda Marcelo, Pahar Bapi, Marx Preston A
Tulane National Primate Research Center, Covington, Louisianna, USA.
AIDS. 2007 Nov 30;21(18):2377-85. doi: 10.1097/QAD.0b013e3282f08b32.
: 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.
: 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.
: 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.
: 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.
利用感染猴免疫缺陷病毒（SIVmac）的中国恒河猴（Ch Rh）来表征长期无进展者（LTNP）状态的免疫病理学。所解决的关键问题是，LTNP在急性感染期间是否经历黏膜CD4 T细胞的早期快速丧失，以及他们维持LTNP状态的机制。
Ch Rh感染SIVmac239。在SIV感染期间，使用多色流式细胞术分析血液、淋巴结和肠道组织中的T淋巴细胞亚群。通过分支DNA分析监测血浆病毒载量。对两只LTNP用抗CD8抗体进行体内治疗以清除CD8细胞。
16只感染SIVmac239的ChRh中有31%（5/16）长达6年病毒载量较低，属于LTNP。LTNP和疾病进展者在感染前肠道记忆CD4/CCR5 T细胞（靶细胞）水平相似，两组均出现早期且严重的靶细胞耗竭。LTNP的特点是黏膜靶细胞逐渐恢复，感染后6个月时明显可见。两只LTNP体内CD8细胞清除后，一只LTNP（V542）在抗CD8治疗后诱发了艾滋病，另一只（AJ07）在病毒血症短暂上升后仍保持健康。
LTNP和疾病进展者靶细胞的早期破坏程度相当，且不能预测临床结果。肠道靶细胞的恢复与长期无进展相关。CD8 T细胞可能在维持LTNP状态中起关键作用。
