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

Despite substantial advances in our understanding of CD4(+)CD25(+) regulatoryT cells, a possible equivalent regulatory subset within the CD8(+) T cell population has received less attention. We now describe novel human CD8(+)/TCR alpha beta(+) 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 TGF beta 1, 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.