Open AccessDe novogeneration of antigen-specific CD4+CD25+regulatory T cells from human CD4+CD25–cells
Author(s) -
Mindi Walker,
Bryan. Carson,
Gerald T. Nepom,
Steven F. Ziegler,
Jane H. Buckner
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0407691102
Subject(s) - il 2 receptor , antigen , biology , t cell , epitope , antigen presenting cell , microbiology and biotechnology , t lymphocyte , bystander effect , cytotoxic t cell , interleukin 21 , cd40 , cd28 , immune system , immunology , in vitro , biochemistry
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.