PACTG: P1006

PACTG：P1006

• 批准号: 7378803
• 负责人: Deborah Persaud
• 金额: $ 0.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378803
• 关键词: PACTG; P1006

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).

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。在 HIV-1 感染儿童开始高效抗逆转录病毒治疗 (HAART) 后，CD4 T 细胞显着增加。然而，目前还没有大量已发表的儿童研究来描述 HIV 感染儿童在 HAART 期间免疫恢复的动态。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) 严重免疫缺陷的儿童在开始 HAART 后 1-2 年内将产生大量 CD4 T 细胞（特别是幼稚表型的细胞）； 2）T细胞的恢复取决于治疗前3个月病毒载量的显着降低，但不需要治疗6个月后持续抑制病毒复制； 3）不会因记忆T细胞的克隆删除而发生免疫反应的自发恢复； 4) 新获得的 CD4 T 细胞可以在抗原暴露后产生反应。因此，本研究将检查 HAART 启动后再生的 T 细胞表型，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。需要解决的一个具体问题是，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，而是可能源自最近被训练成为记忆细胞的初始T细胞。为了进一步剖析 HAART 期间新产生的 T 细胞的功能，将测试细胞介导的针对回忆抗原（破伤风）、初级免疫原（甲型肝炎）和环境抗原（念珠菌）的免疫反应。新生成的 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）加强免疫做出反应的能力。