CD4-CD8αα subset of CD1d-restricted NKT cells controls T cell expansion

被引:49
作者
Ho, LP
Urban, BC
Jones, L
Ogg, GS
McMichael, AJ
机构
[1] John Radcliffe Hosp, Med Res Council Human Immunol Unit, Weatherall Inst Mol Med, Oxford, England
[2] Churchill Hosp, Oxford Ctr Resp Med, Oxford, England
基金
英国医学研究理事会;
关键词
D O I
10.4049/jimmunol.172.12.7350
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Valpha24 invariant (Valpha24i) CD1d-restricted NKT cells are widely regarded to have immune regulatory properties. They are known to have a role in preventing autoimmune diseases and are involved in optimally mounted immune responses to pathogens and tumor cells. We were interested in understanding how these cells provide protection in autoimmune diseases. We first observed, using EBV/MHC I tetrameric complexes, that expansion of Ag-specific cells in human PBMCs was reduced when CD1d-restricted NKT cells were concomitantly activated. This was accompanied by an increase in a CD4(-)CD8alphaalpha(+) subset of Valpha24i NKT cells. To delineate if a specific subset of NKT cells was responsible for this effect, we generated different subsets of human CD4(-) and CD4(+) Valpha24i NKT clones and demonstrate that a CD4(-)CD8alphaalpha(+) subset with highly efficient cytolytic ability was unique among the clones in being able to suppress the proliferation and expansion of activated T cells in vitro. Activated clones were able to kill CD1d-bearing dendritic or target cells. We suggest that one mechanism by which CD1d-restricted NKT cells can exert a regulatory role is by containing the proliferation of activated T cells, possibly through timely lysis of APCs or activated T cells bearing CD1d.
引用
收藏
页码:7350 / 7358
页数:9
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