Functional analysis of human NKT cells and myeloid DCs within murine SCID hosts

描述（由申请人提供）：NKT细胞包括一个小的T细胞亚群，似乎对免疫功能具有深远和显著不同的影响。NKT细胞影响下游免疫反应的机制仍然知之甚少。在我们的初步研究中，我们已经观察到人类NKT细胞在体外诱导新鲜外周血单核细胞分化为树突状细胞（dc）。由此产生的dc具有独特的调节表型，并且似乎沉默mhc限制性T细胞激活。因此，我们假设促进调节性dc的分化是NKT细胞广泛影响免疫反应的一种机制。然而，目前尚不清楚NKT细胞是否能在体内发挥这一功能。在这里，我们建议i)测试人类NKT细胞在转移到SCID小鼠宿主后引导人类单核细胞分化为DCs的能力，ii)研究NKT细胞在SCID小鼠中诱导的人类DCs的功能特性。摘要：本项目拟使用体内SCID小鼠系统来研究人类NKT细胞在促进单核细胞分化为dc方面的功能，并测试由此产生的dc的功能特性。

DESCRIPTION (provided by applicant): NKT cells comprise a small T cell subset that appears to have far-reaching and remarkably varied effects on immune function. The mechanisms by which NKT cells affect down-stream immune responses remain poorly understood. In our preliminary studies we have observed that human NKT cells direct fresh peripheral blood monocytes to differentiate into dendritic cells (DCs) in vitro. The resulting DCs have a unique regulatory phenotype, and appear to silence MHC-restricted T cell activation. Hence, we hypothesize that promoting the differentiation of regulatory DCs is one mechanism by which NKT cells can broadly affect immune responses. However, it remains unclear whether NKT cells can perform this function in vivo. Here we propose i) to test the ability of human NKT cells to direct human monocyte differentiation into DCs after transfer into SCID-mouse hosts, and ii) to investigate the functional properties of NKT cell-induced human DCs within the SCID mice. Abstract Narrative: This grant proposes to use an in vivo SCID mouse system to investigate the functions of human NKT cells in promoting monocytes to differentiate into DCs, and to test the functional properties of the resulting DCs.