PACTG: P1006

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在HIV-1感染的儿童中，在开始高效抗逆转录病毒治疗（HAART）后，CD 4 T细胞显著增加。然而，目前还没有大型的儿童研究报告描述HAART治疗期间HIV感染儿童的免疫恢复动态。需要一项多中心研究来检查HAART启动后再生的T细胞的表型和功能，以进一步评估初步数据支持的几个假设。这些初步数据支持以下假设：1）严重免疫耗竭的儿童将产生大量的CD 4 T细胞2）T细胞的恢复依赖于治疗前3个月内病毒载量的显著降低，但不需要治疗6个月后病毒复制的持续抑制; 3）由于记忆T细胞的克隆缺失，免疫应答的自发恢复将不会发生;以及4）新获得的CD 4 T细胞可以在抗原暴露后产生应答。因此，本研究将检查HAART启动后再生的T细胞的表型，并通过评估T细胞对新抗原和回忆抗原的反应来评估其功能。一个需要解决的具体问题是，当外周记忆T细胞可能增加时，儿童的免疫功能是否会在治疗早期恢复。或者，记忆T细胞克隆可能不是来自外周记忆T细胞的扩增，而是可能来源于最近被训练成为记忆细胞的幼稚T细胞。为了进一步分析HAART期间新产生的T细胞的功能，将检测对回忆抗原（破伤风）、初级免疫原（甲型肝炎）和环境抗原（念珠菌）的细胞介导的免疫应答。新产生的T细胞对破伤风类毒素和新抗原T细胞依赖性抗原（甲型肝炎）的加强免疫应答的能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A significant increase in CD4 T cells occurs after the initiation of highly active antiretroviral therapy (HAART) in HIV-1 infected children. However, there are no large published studies in children delineating the dynamics of immune recovery in HIV-infected children during HAART. A multi-center study powered to examine the phenotype and function of T cells regenerated post - HAART initiation is needed to further assess several assumptions supported by the preliminary data. These preliminary data support the assumptions that 1) children with severe immunodepletion will develop significant numbers of CD4 T cells (particularly those of the naive phenotype) for 1-2 years after initiating HAART; 2) the recovery of T cells is dependent on a significant decrease in viral load in the first 3 months of therapy but does not require sustained suppression of viral replication after 6 months of therapy; 3) the spontaneous recovery of immunologic responses will not occur due to the clonal deletion of memory T cells; and 4) newly acquired CD4 T cells can develop responses upon antigenic exposure. This study will therefore examine the phenotype of T cells regenerated post initiation of HAART and assess their function by evaluating T cell responses to new antigens and recall antigens. One specific question to be addressed will be whether recovery of immunologic function in children occurs early in therapy when an increase in peripheral memory T cells is likely to occur. Alternatively, memory t cell clones may not be from expansion of peripheral memory T cells but rather may be derived from naive T cells that were recently educated to become memory cells. In order to further dissect function of newly generated T cells during HAART, cell mediated immune responses to a recall antigen (tetanus), a primary immunogen (hepatitis A) and an environmental antigen (Candida), will be tested. The ability of the newly generated T cells to respond to booster immunizations with tetanus toxoid and a new antigen T cell dependent antigen (hepatitis A).