De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells.
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.
Walker
Mindi R
MR
Diabetes Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA.
Carson
Bryan D
BD
Nepom
Gerald T
GT
Ziegler
Steven F
SF
Buckner
Jane H
JH
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D015375:Receptors, Interleukin-2