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

AUTOR(ES)

Walker, Mindi R.

FONTE

National Academy of Sciences

RESUMO

Antigen-specificity is a hallmark of adaptive T cell-mediated immune responses. CD4+CD25+FOXP3+ regulatory T cells (TR) 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 TR may be useful therapeutically by localizing generalized suppressive activity to tissues expressing select target antigens. Here, we demonstrate that TR 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 TR, 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.

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