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

Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4103-8. doi: 10.1073/pnas.0407691102. Epub 2005 Mar 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunologic Memory / immunology
  • Receptors, Interleukin-2 / immunology*


  • Histocompatibility Antigens Class II
  • Receptors, Interleukin-2