ASSESSMENT OF SIV+ CD4-LOW MANGABEYS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 CD 4 + T细胞耗竭和疾病进展速度加快之间的关联已在人类HIV感染和猕猴猴免疫缺陷病毒（SIV）感染中得到充分证实。在我们的研究之前，尽管血浆病毒载量相似，但观察到SIV感染其天然灵长类宿主（即白眉猴）导致接近正常水平的CD 4 + T细胞。在2000年和2006年从SIV+白眉猴转移血浆后，5只白眉猴表现出CD 4 + T细胞水平下降至低于100个细胞/ul血液，也在淋巴结中观察到。在过去的十年中，这些水平一直保持在18至100个细胞/ul血液之间。通过微量中和试验和血凝抑制，确定所有五只白眉猴都能够对流感疫苗接种产生有效的抗体应答，即使CD 4 + T细胞水平非常低。 在这些白眉猴中观察到的低免疫激活和保留的免疫应答与具有中枢记忆表型的CD 3 + CD 4-CD 8-双阴性T细胞的存在相关，这些T细胞能够产生Th 1，Th 2和Th 17细胞因子。 这些研究表明，在SIV感染的自然宿主中，CD 4 + T细胞耗竭不一定导致免疫功能障碍。 事实上，SIV感染的白眉猴似乎并不完全依赖于CD 4 + T细胞来维持免疫力，并将该物种中的双阴性T细胞鉴定为能够执行CD 4样辅助功能的潜在亚群。 这些双阴性T细胞的进一步表征正在进行中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The association between CD4+ T-cell depletion and an accelerated rate of disease progression is well established for HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques. Prior to our studies, SIV infection in its natural primate host (i.e. sooty mangabeys) was observed to result in near normal levels of CD4+ T-cells despite similar plasma viral loads. Following transfer of plasma from an SIV+ mangabey in 2000 and 2006, five mangabeys exhibited a decline in CD4+ T cell levels to below 100 cells/ul of blood, also observed in lymph nodes. These levels have remained between 18 and 100 cells/ul of blood for the past decade. Through microneutralization assays and hemaglutination inhibition it was determined that all five mangabeys were able to mount effective antibody responses to the influenza vaccination, even with the very low levels of CD4+ T cells. Low immune activation and preserved immune responses observed in these mangabeys were associated with the presence of CD3+CD4-CD8- double-negative T cells with a central memory phenotype that are capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that CD4+ T cell depletion in SIV-infected natural hosts need not result in immune dysfunction. Indeed, SIV-infected mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells in this species as a potential subset capable of performing CD4-like helper functions. Further characterization of these double-negative T cells is underway.