ROLE OF NATURAL KILLER T (NKT) LYMPHOCYTES IN SOOTY MANGABEYS

这个子项目是许多利用 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。 自然杀伤T（NKT）淋巴细胞是一个独特的T淋巴细胞亚群，具有不变的TCR Valpha链，并识别由非多态性CD 1d分子呈递的配体。 在功能上，CD 1d反应性NKT细胞可以分泌大量的Th-1和Th-2型细胞因子，包括IL-10，并且是先天免疫系统的早期效应物。 由于它们分泌的不同细胞因子，NKT细胞可能在调节HIV和SIV感染中的免疫激活中发挥作用。 黑白眉猴是SIV的天然宿主，不会发展为艾滋病。 SIV感染在其天然宿主中的一个关键区别特征是不存在异常免疫激活。 在这个项目中，我们正在调查是否NKT细胞是负责缺乏异常的免疫激活在自然SIV感染mangabey。 在对50只SIV阴性和50只SIV感染的白眉猴的横断面分析中，外周血的流式细胞术评价显示，在大约50%的白眉猴中，循环Valpha 24阳性CDld-四聚体阳性NKT淋巴细胞的可检测频率。 在功能上，mangabey NKT细胞以CDld限制性方式分泌IFN-γ、IL-2、IL-4、IL-10和IL-13，并且还能够脱粒，这表明具有免疫调节和细胞溶解功能。 它们在SIV感染的白眉猴中似乎也没有耗尽。 SIV感染的自然和非自然宿主中NKT淋巴细胞的比较正在进行中。

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. Natural Killer T (NKT) lymphocytes are a unique subset of T lymphocytes that have an invariant TCR Valpha chain and recognize ligands presented by the nonpolymorphic CD1d molecule. Functionally, CD1d-reactive NKT cells can secrete large amounts of both Th-1 and Th-2 type cytokines, including IL-10, and are early effectors of the innate immune system. By virtue of the diverse cytokines that they secrete, NKT cells may play a role in modulating immune activation in HIV and SIV infection. Sooty mangabeys are a natural host of SIV that do not progress to AIDS. A key differentiating feature of SIV infection in its natural host is the absence of aberrant immune activation. In this project we are investigating whether NKT cells are responsible for the lack of aberrant immune activation in naturally SIV-infected sooty mangabeys. In a cross-sectional analysis of 50 SIV-negative and 50 SIV-infected sooty mangabeys, flow cytometric evaluation of eripheral blood has revealed detectable frequencies of circulating Valpha24positive CDld-tetramer positive NKT lymphocytes in roughly 50% of sooty mangabeys. Functionally, mangabey NKT cells secrete IFN-gamma, IL-2, IL-4, IL-10, and IL-13 in a CD1d-restricted manner, and are also capable of degranulation suggesting both immunoregulatory and cytolytic functions. They also do not appear to be depleted in SIV-infected sooty mangabeys. Comparison of NKT lymphocytes in natural and non-natural hosts of SIV infection is in progress.