CD30 discriminates heat shock protein 60-induced FOXP3+ CD4+ T cells with a regulatory phenotype

J Immunol. 2010 Aug 15;185(4):2071-9. doi: 10.4049/jimmunol.0901901. Epub 2010 Jul 14.


In many animal models, the manifestations of inflammatory diseases can be prevented by the adoptive transfer of CD4(+)FOXP3(+) regulatory T cells (Tregs). CD4(+)FOXP3(+) Tregs can be obtained by isolation and expansion of polyclonal naturally occurring Tregs or by Ag-specific activation of CD4(+)CD25(-)FOXP3(-) T cells. Two major obstacles are hampering the translation of this latter protocol into therapeutic application. First, there is a lack of knowledge on relevant autoantigens. Second, the resulting population is contaminated with activated CD4(+) T cells that transiently express Forkhead box P3 but gain no regulatory function. Therefore, these cells may not be safe for clinical application. In this study, we demonstrate that highly suppressive FOXP3(+) Tregs can be induced in vitro by the activation of CD4(+)CD25(-) T cells with the self-Ag human 60-kDa heat shock protein (HSP60). The activation induced suppressive FOXP3(+) Tregs can be distinguished by surface expression of CD30 from nonsuppressive FOXP3(+) effector cells. We confirm that the induced CD30(+)FOXP3(+) Tregs recognize HSP60 epitopes and that the induction of Tregs by HSP60 is enhanced by signaling via TLR4 on APCs. These findings have implications for the generation and isolation of pure populations of Ag-specific Tregs, with the potential to prevent and treat human inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chaperonin 60 / immunology
  • Chaperonin 60 / pharmacology*
  • Cytokines / metabolism
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / drug effects
  • Humans
  • Immunophenotyping
  • Ki-1 Antigen / genetics
  • Ki-1 Antigen / immunology*
  • Ki-1 Antigen / metabolism
  • Lymphocyte Activation / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism


  • Chaperonin 60
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Ki-1 Antigen
  • TLR4 protein, human
  • Toll-Like Receptor 4