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，我们观察到人NKT细胞在体外引导新鲜的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，似乎能沉默MHC限制的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机制之一。然而，目前尚不清楚NKT细胞是否能在体内发挥这一功能。在此，我们建议：1)检测人NKT细胞在SCID-小鼠宿主体内向人单核细胞定向分化为DC的能力；2)研究NKT细胞诱导人DC在SCID小鼠体内的功能特性。摘要简介：这项资助建议使用活体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.