CHANGES IN LYMPHOCYTE POPULATIONS AND ARCHITECTURE BEFORE AND DURING HIV-1 THERA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 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 研究中心，而研究中心不一定是研究者所在的机构。 越来越多的人认识到，高达25%的人开始HAART，谁有病毒抑制，有一个微不足道的免疫重建水平。 对HIV阳性者淋巴组织的检查显示，几乎每一位接受检查的患者淋巴库中的CD 4 + T细胞都出现了早期和显著的耗竭。 初步研究表明，所观察到的免疫重建的可变性与LT结构损伤的测量相关。 我们认为，在HIV-1感染时，某些个体会发生慢性炎症过程，通过胶原蛋白沉积和网硬蛋白网络破坏TZ生态位。 本研究的目的是通过对ART初治个体的前瞻性研究详细检查这一假设。 我们将在开始HAART前后的多个时间点收集患者的LT。 我们将确定治疗前TZ中胶原蛋白量的单次测量是否可以预测作为免疫重建指标的CD 4细胞计数的变化。 我们将确定这些架构变化是否可以通过HAART逆转。 我们将检查LT和外周血中CD 4+细胞的表型亚群，在开始HAART之前和之后的多个时间点，以确定重新填充LT的CD 4 + T细胞的来源和命运。成功的collegen可能预测HAART的成功，并建议在治疗开始前进行reoutine活检可能有助于确定开始治疗的最佳时机。 此外，这些研究可能为HAART免疫重建的机制以及为什么有些人有不完全的反应提供额外的见解。 我们请求允许使用GCRC资源和护理服务，用于第0天和第3天之间的住院患者、住院患者和门诊患者抽血以及门诊手术的术前和恢复。

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. There is a growing appreciation of the fact that up to 25% of people initiating HAART, who have virologic suppression, have an insignificant level of immune reconstitution. Examination of lymphatic tissues from HIV+ persons reveals an early and significant depletion of CD4+ T-cells in the lymphatic reservoir in virtually every patient examined. Preliminary studies have suggested the observed variablility in immune reconstitution is correlated with measures of damage to the LT architecture. We believe that a process of chronic inflammation occurs in some individuals at the time of HIV-1 infection that disrupts the TZ niche through deposition of collagen and destruction of the reticulin network. The goal of this study is to examine this hypothesis in detail with a prospective study of ART naive individuals. We will collect LT from patients at multiple time points before and after starting HAART. We will determine if a single measurement of the amount of collagen in the TZ before treatment will predict the change in CD4 cell count as a measure of immune reconstitution. We will determine if these architectural changes are reversible with HAART. We will examine the phenotype subsets of CD4+ cells in LT and peripheral blood at multiple time points before and after starting HAART to determine the source and fate of CD4+ T cells that repopulate the LT. Successful collegen might predict success of HAART and suggest that reoutine biopsy before therapy is begun might help to determine optimal timing of initiation of therapy. In addition, these studies may provide additional insight into the mechanism of immune reconstitution with HAART and why some individuals have incomplete responses. We are requesting permission to use the GCRC resources and nursing services for the inpatient stays between Day 0 and Day 3, for both inpatient and outpatient blood draws, and for pre-op and recovery of the outpatient surgical procedures.