De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4-CD25- cells

被引:246
作者
Walker, MR
Carson, BD
Nepom, GT
Ziegler, SF
Buckner, JH [1 ]
机构
[1] Benaroya Res Inst Virginia Mason, Diabet Program, Seattle, WA 98101 USA
[2] Benaroya Res Inst Virginia Mason, Program Immunol, Seattle, WA 98101 USA
[3] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
关键词
autoimmunity; T lymphocytes; tolerance; suppression; anergy;
D O I
10.1073/pnas.0407691102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Antigen-specificity is a hallmark of adaptive T cell-mediated immune responses. CD4(+)CD25(+)FOXP3(+) regulatory T cells (T-R) also require activation through the T cell receptor for function. Although these cells require antigen-specific activation, they are generally able to suppress bystander T cell responses once activated. This raises the possibility that antigen-specific T-R may be useful therapeutically by localizing generalized suppressive activity to tissues expressing select target antigens. Here, we demonstrate that T-R specific for particular peptide-MHC complexes can be generated from human CD4(+)CD25(-) T cells in vitro and isolated by using HILA class II tetramers. influenza hemagglutinin epitopes were used to generate hemagglutinin-specific T-R, which required cognate antigen for activation but which subsequently suppressed noncognate bystander T cell responses as well. These findings have implications for the generation of therapeutic regulatory T cells in disease, and also suggest an important mechanism by which T cells may be regulated at the site of inflammation.
引用
收藏
页码:4103 / 4108
页数:6
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