PROJECT 3: CLINICAL TRIALS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。T细胞可以产生多种不同的细胞因子，其共表达谱随其成熟状态的不同而明显不同。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例HAART和20例HAART受者的HIV特异性T细胞进行了横断面评估。这些研究表明，感染者的CD4和CD8T细胞都存在产生IL-2的缺陷，随着抗逆转录病毒药物治疗的进行，这种缺陷可以部分修复。感染患者的CD4T细胞正在进一步研究其细胞因子的产生模式。总体而言，与未经治疗的患者相比，长期无进展患者的HIV特异性CD4反应似乎更具多功能性，或能够产生各种细胞因子。用抗逆转录病毒药物治疗可以部分恢复多功能T细胞的存在。NIH HIV疫苗试验网络将在我们的分支B疫苗1a/1b阶段试验期间产生的样本上进行辅助分析，并努力建立T细胞反应的GLP分析。GLP检测包括胸腺嘧啶核苷增殖法、ELISPOT法等。IL-2和细胞内细胞因子染色检测干扰素？和IL-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.