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

作者：Mindi Walker, Bryan D Carson, Gerald T. Nepom, Steven F. Ziegler, Jane Hoyt Buckner · 发表于：Proceedings of the National Academy of Sciences · 年份：2005 · DOI：10.1073/pnas.0407691102 · 被引用次数：283 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

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 HLA 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.