IMMUNOBIOLOGY OF SAIDS-ASSOCIATED LYMPHOMAS

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。我们正在继续与劳拉·列维博士合作，研究感染siv和未感染siv的恒河猴的淋巴瘤。到目前为止，我们已经确定了50例猿类艾滋病相关淋巴瘤（sARL）和108例对照动物，这些动物在SIV接种时的物种、性别和年龄相匹配。然后，我们收集了所有动物的纵向实验室和临床数据，包括生存时间、绝对和相对b细胞和t细胞计数、疾病过程中b细胞和t细胞变化率、淋巴样增生的临床证据和外周血抗原血症。采用病例对照法对资料进行统计学分析。统计分析是最近完成的，证明是详尽无遗的。结果产生了至少500页的输出，我们希望在接下来的几个月里对其进行审查和解释。我们正在寻找实验室或临床结果与早期疾病发病之间的统计学显著相关性，以便这些结果可能对淋巴瘤的后期发展具有预测价值。在过去的资助年度里，我们在剖析控制arl衍生细胞生长的复杂调控网络方面取得了实质性进展。我们重点研究了在类人猿ARL （sARL）中表达的两种细胞因子，即IL-6和tgf - β 1的独立和相互作用影响。具体而言，我们的研究表明，sarl衍生的细胞系LCL8664对TGF-beta1的生长抑制敏感，IL-6似乎通过多种机制增加增殖和细胞活力，包括部分阻断TGF-beta1诱导的细胞周期阻滞和凋亡。

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. We are continuing our collaborative project with Dr. Laura Levy in examining lymphomas in SIV-infected and uninfected rhesus macaques. To date, we have identified 50 cases of simian AIDS-related lymphoma (sARL) and 108 control animals age-matched for species, gender and age at SIV inoculation. We then assembled longitudinally collected laboratory and clinical data on all animals relating to survival time, absolute and relative B-cell and T-cell counts, rate of B-cell and T-cell change over the disease course, clinical evidence of lymphoid hyperplasia, and peripheral blood antigenemia. The data were than analyzed statistically in a case-control manner. The statistical analysis was recently completed, and proved to be exhaustive. At least 500 pages of output resulted, which we expect to review and interpret over the next few months. We are seeking statistically significant correlations between laboratory or clinical findings and early disease onset, such that such findings might have predictive value for the later development of lymphoma. Over the past funding year, we have made substantial progress in dissecting the complex network of regulation that controls the growth of ARL-derived cells. We focused on the independent and interacting influences of two cytokines that are expressed in simian ARL (sARL), i.e., IL-6 and TGF-beta1. Specifically, our studies have shown the sARL-derived cell line, LCL8664, was sensitive to growth inhibition by TGF-beta1, that IL-6 appears to increase proliferation and cell viability through multiple mechanisms, including partially blocking the cell cycle arrest and apoptosis induced by TGF-beta1.