Kaur A, Rosenzweig M, Johnson R P
Division of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772-9102, USA.
Philos Trans R Soc Lond B Biol Sci. 2000 Mar 29;355(1395):381-90. doi: 10.1098/rstb.2000.0578.
Infection with the human immunodeficiency virus results in profound perturbations in immunological memory, ultimately resulting in increased susceptibility to opportunistic infections and acquired immunodeficiency syndrome (AIDS). We have used rhesus macaques infected with the simian immunodeficiency virus (SIV) as a model to understand better the effects of AIDS virus infection on immunological memory. Acute infection with SIV resulted in significant deficits in CD4+ helper responses to cytomegalovirus (CMV) as well as CMV-specific cytotoxic T-lymphocyte and neutralizing antibody responses. Reactivation of CMV was associated with high levels of SIV replication and suppression of both T-helper and cytotoxic responses to CMV. We have also studied the effects of SIV infection on T-cell turnover in non-human primates. T-cell turnover was evaluated using the nucleoside analogue bromodeoxyuridine (BrdU) in combination with five-colour flow cytometric analysis. T cells in normal animals turned over at relatively rapid rates, with memory cells turning over more quickly than naive cells. In SIV-infected animals, the labelling and elimination rates of both CD4+ and CD8+ BrdU-labelled cells were increased by two- to threefold compared with normal controls. Further analysis of immunological memory in non-human primates should offer the opportunity to extend immunological insights from murine models to the pathogenesis and prevention of AIDS.
感染人类免疫缺陷病毒会导致免疫记忆出现严重紊乱，最终导致对机会性感染和获得性免疫缺陷综合征（AIDS）的易感性增加。我们利用感染了猿猴免疫缺陷病毒（SIV）的恒河猴作为模型，以更好地了解艾滋病病毒感染对免疫记忆的影响。SIV急性感染导致CD4 +辅助性T细胞对巨细胞病毒（CMV）的反应以及CMV特异性细胞毒性T淋巴细胞和中和抗体反应出现显著缺陷。CMV的重新激活与高水平的SIV复制以及对CMV的T辅助性和细胞毒性反应的抑制有关。我们还研究了SIV感染对非人灵长类动物T细胞更新的影响。使用核苷类似物溴脱氧尿苷（BrdU）结合五色流式细胞术分析来评估T细胞更新。正常动物中的T细胞以相对较快的速度更新，记忆细胞的更新速度比幼稚细胞更快。在感染SIV的动物中，与正常对照相比，CD4 +和CD8 + BrdU标记细胞的标记和消除率增加了两到三倍。对非人灵长类动物免疫记忆的进一步分析应该为将免疫见解从鼠模型扩展到艾滋病的发病机制和预防提供机会。
