NKT CELLS AS MODULATORS OF IMMUNE ACTIVATION IN SOOTY MANGABEYS

NKT 细胞作为乌白眉猴免疫激活的调节剂

• 批准号: 7958364
• 负责人: Amitinder Kaur
• 金额: $ 19.97万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958364
• 关键词: Acquired Immunodeficiency Syndrome; Autoimmune Process; Autoimmunity; Cercocebus; Cercocebus atys; Computer Retrieval of Information on Scientific Projects Database; Cross-Sectional Studies; Diabetes Mellitus; Evaluation; Frequencies; Funding; Grant; HIV; HIV Infections; Human; Immune; Immune system; Inbred NOD Mice; Infection; Institution; Interferon Type II; Interleukin-10; Interleukin-13; Interleukin-2; Interleukin-4; Ligands; Macaca mulatta; Mus; New England; Play; Primates; Research; Research Personnel; Resources; Role; SIV; Source; T-Lymphocyte; T-Lymphocyte Subsets; United States National Institutes of Health; base; cytokine; immunopathology; killer T cell; peripheral blood; prevent

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. NKT cells have been shown to protect against autoimmunity and immunopathology in diabetes-prone NOD mice and prevent experimental autoimmune encepholomyelitis in mice. In humans, invariant NKT cells are mainly CD4-positive and CD4/8 double negative T lymphocytes and are lost early in HIV infection. 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. Flow cytometric evaluation of peripheral blood has revealed detectable frequencies of circulating Valpha24positive CDld-tetramer positive NKT lymphocytes in sooty mangabeys but not rhesus macaques. 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 cytolytic function. Cross-sectional analysis of NKT cells in 60 SIV-negative and 46 SIV-infected sooty mangabey is in progress.

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。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他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。 NKT细胞已被证明可以保护易患糖尿病的NOD小鼠免受自身免疫和免疫病理学的影响，并预防小鼠的实验性自身免疫性脑脊髓炎。 在人类中，不变的NKT细胞主要是CD 4阳性和CD 4/8双阴性T淋巴细胞，并在HIV感染早期丢失。 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。 流式细胞术评价外周血显示循环中Valpha 24阳性CDld-四聚体阳性NKT淋巴细胞在正常白眉猴中的可检测频率，而在恒河猴中则没有。 在功能上，mangabey NKT细胞以CD 1d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，表明细胞溶解功能。 对60只SIV阴性和46只SIV感染的白眉猴的NKT细胞的横断面分析正在进行中。