Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host
Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host
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DOI：
10.4049/jimmunol.179.5.3047
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Sodora, Donald L.
中科院分区：
文献类型：
--
作者：
Milush, Jeffrey M.;Reeves, Jacqueline D.;Sodora, Donald L.
外周血CD4(+) T细胞计数是评估HIV感染者疾病进展和抗逆转录病毒治疗需求的关键指标。最近的研究表明，急性感染期间粘膜 CD4+ T 细胞急剧减少，而慢性致病性 HIV 和 SIV 感染期间仍维持这种情况。在 SIV 感染的自然宿主（例如乌白眉猴（Cercocebus atys））感染期间观察到不同的临床疾病过程，它们通常不会发展为艾滋病。先前的研究已经确定，SIV+白眉猴通常保持健康的CD4+T细胞水平，尽管其病毒复制能力与HIV感染者相当。在这项研究中，我们发现两只白眉猴在感染后43周或71周后出现了多向性（R5/X4/R8使用）SIV感染，这与在没有艾滋病临床症状的情况下CD4+T细胞（5-80个细胞/μl血液）的极端、持续（>5.5年）和普遍损失有关。这项研究表明，血液和粘膜组织中广泛的 CD4(+) T 细胞耗竭不足以在该自然宿主物种中诱发艾滋病。相反，艾滋病发病机制似乎是多种异常免疫参数的累积结果，包括CD4(+) T 细胞耗竭、全身免疫激活和非CD4(+) T 细胞耗竭/功能障碍。因此，这些数据为研究多方面的治疗策略提供了理论依据，以防止进展为艾滋病，即使在 CD4 急剧减少后，HIV + 人类也可以像 SIV + 白眉猴一样正常生存。
Peripheral blood CD4(+) T cell counts are a key measure for assessing disease progression and need for antiretroviral therapy in HIV-infected patients. More recently, studies have demonstrated a dramatic depletion of mucosal CD4(+) T cells during acute infection that is maintained during chronic pathogenic HIV as well as SIV infection. A different clinical disease course is observed during the infection of natural hosts of SIV infection, such as sooty mangabeys (Cercocebus atys), which typically do not progress to AIDS. Previous studies have determined that SIV+ mangabeys generally maintain healthy levels of CD4(+) T cells despite having viral replication comparable to HIV-infected patients. In this study, we identify the emergence of a multitropic (R5/X4/R8-using) SIV infection after 43 or 71 wk postinfection in two mangabeys that is associated with an extreme, persistent (>5.5 years), and generalized loss of CD4(+) T cells (5-80 cells/mu l of blood) in the absence of clinical signs of AIDS. This study demonstrates that generalized CD4(+) T cell depletion from the blood and mucosal tissues is not sufficient to induce AIDS in this natural host species. Rather, AIDS pathogenesis appears to be the cumulative result of multiple aberrant immunologic parameters that include CD4(+) T cell depletion, generalized immune activation, and depletion/dysfunction of non-CD4(+) T cells. Therefore, these data provide a rationale for investigating multifaceted therapeutic strategies to prevent progression to AIDS, even following dramatic CD4 depletion, such that HIV+ humans can survive normal life spans analogous to what occurs naturally in SIV+ mangabeys.