Autoreactive human peripheral blood CD8+ T cells with a regulatory phenotype and function

Eur J Immunol. 2005 Oct;35(10):2896-908. doi: 10.1002/eji.200526162.


Despite substantial advances in our understanding of CD4+ CD25+ regulatory T cells, a possible equivalent regulatory subset within the CD8+ T cell population has received less attention. We now describe novel human CD8+/TCR alphabeta+ T cells that have a regulatory phenotype and function. We expanded and cloned these cells using autologous LPS-activated dendritic cells. The clones were not cytolytic, but responded in an autoreactive HLA class I-restricted fashion, by proliferation and production of IL-4, IL-5, IL-13 and TGFbeta1, but not IFN-gamma. They constitutively expressed CD69 and CD25 as well as molecules associated with CD4+ CD25+ regulatory T cells, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and Foxp3. They suppressed IFN-gamma production and proliferation by CD4+ T cells in vitro in a cell contact-dependent manner, which could be blocked using a CTLA-4-specific mAb. They were more readily isolated from patients with ankylosing spondylitis and may therefore be up-regulated in response to inflammation. We suggest that they are the CD8+ counterparts of CD4+ CD25+ regulatory T cells. They resemble recently described CD8+ regulatory cells in the rat that were able to abrogate graft-versus-host disease. Likewise, human HLA-restricted CD8+ regulatory T cells that can be cloned and expanded in vitro may have therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Antigens, Differentiation / immunology
  • Blotting, Western
  • CD8-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • Phenotype
  • Receptors, Interleukin-2 / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, rat
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, Interleukin-2