IMMUNOBIOLOGY OF SAIDS-ASSOCIATED LYMPHOMAS

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。我们正在继续我们与Laura Levy博士的合作项目，检查感染SIV和未感染SIV的恒河猴的淋巴瘤。到目前为止，我们已经确认了50例猴艾滋病相关淋巴瘤(SAHL)病例和108只对照动物，在接种SIV时，它们的年龄与物种、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，这些数据涉及存活时间、B细胞和T细胞的绝对和相对计数、B细胞和T细胞在病程中的变化率、淋巴组织增生的临床证据以及外周血液抗原血症。采用病例对照的方法对数据进行统计分析。最近完成了统计分析，并被证明是详尽的。结果产生了至少500页的产出，我们预计将在未来几个月内审查和解读这些产出。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上的显著相关性，以便这些发现可能对淋巴瘤的后期发展具有预测价值。在过去的一年里，我们在剖析控制ARL来源细胞生长的复杂调控网络方面取得了实质性进展。我们重点研究了在猿猴ARL中表达的两种细胞因子，即IL-6和TGF-β1的独立和相互作用的影响。特别是，我们的研究表明SARL来源的细胞株LCL8664对转化生长因子-β1的生长抑制很敏感，IL-6似乎通过多种机制促进细胞增殖和存活，包括部分阻断转化生长因子-β1诱导的细胞周期停滞和凋亡。

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.