PROJECT 3: CLINICAL TRIALS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。T细胞可以产生多种不同的细胞因子，它们的共表达谱根据它们的成熟状态而显著不同。许多因素，包括抗原的持续水平，可以影响T细胞的成熟状态及其细胞因子的共表达谱。为了确定HIV-1感染者CD4和CD8 T细胞的细胞因子共表达谱以及血浆病毒血症的影响，我们对19名HAART感染者和20名HAART接受者的hiv特异性T细胞进行了横断面评估。这些研究表明，感染患者的CD4和CD8 T细胞在产生IL-2方面都存在缺陷，并且随着抗逆转录病毒药物治疗的时间推移，这种缺陷可以部分地被CD4 T细胞修复。正在进一步研究感染患者的CD4 T细胞的细胞因子产生模式。总的来说，在长期无进展的患者中，hiv特异性CD4反应似乎比未经治疗的患者更多功能，或能够产生多种细胞因子。抗逆转录病毒药物治疗部分恢复了多功能T细胞的存在。在NIH HIV疫苗试验网络进行的我们的进化支B疫苗的1a/1b期试验中将产生的样品的辅助分析中，我们还努力建立针对T细胞反应的GLP分析。GLP检测包括胸腺嘧啶增殖检测、IFN-？IL-2和细胞内细胞因子染色IFN-？和2。

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. T cells can produce multiple different cytokines and their co-expression profiles vary significantly depending on their maturation state. Many factors, including the persisting levels of antigen, can influence the maturation state of T cells and their cytokine co-expression profile. To determine the cytokine co-expression profile of CD4 and CD8 T cells from HIV-1 infected individuals and the influence of plasma viremia, we conducted a cross-sectional evaluation of HIV-specific T cells from 19 HAART na¿ve and 20 HAART recipients. These studies revealed that both CD4 and CD8 T cells in infected patients were defective in IL-2 production and that this defect could be partially rescued for CD4 T cells with time on antiretroviral drug treatment. CD4 T cells in infected patients are being further studied for their cytokine production patterns. Overall, the total HIV-specific CD4 response appears to be more polyfunctional, or capable of producing a variety of cytokines, in long term non-progressors than in untreated patients. Treatment with antiretroviral drugs partially restores the presence of polyfunctional T cells. Effort has also been placed on establishing GLP assays for T cell responses in ancillary assays on samples that will be generated during the phase 1a/1b trial of our clade B vaccine by the NIH HIV Vaccine Trials Network. The GLP assays to be conducted include thymidine proliferation assays, ELISPOT assays for IFN-? and IL-2 and intracellular cytokine staining for IFN-? and IL-2.