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

Abstract

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 + /TCRab + 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 TGFb1, but not IFN-c. 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-c 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 HLArestricted CD8 + regulatory T cells that can be cloned and expanded in vitro may have therapeutic applications.

Identification of a human CD8+regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4

“…In humans, autoreactive CD8 ϩ Tregs were characterized by constitutive expression of CD69, CD25, cytotoxic T lymphocyteassociated antigen 4, and FoxP3, and produced IL-4, IL-5, IL-13, and TGF-␤ but not IFN␥ (23). Furthermore, suppressor CD8 ϩ T cell clones from immunologically unresponsive individuals with leprosy suppressed Th1 responses (14,24).…”

Induced peripheral regulatory T cells: The family grows larger

“…In addition to the different CD4 + Treg that have been described, there are reports suggesting that the CD8 + T cell compartment also contains cells with regulatory properties [15][16][17][18][19][20][21]. A report in the present issue of the European Journal of Immunology by Maile et al [22] describes the identification of CD8 + Treg that arise after stimulation with peptide-loaded MHC class I tetramers in vivo.…”

HIV-Specific IL-10-Positive CD8+ T Cells Suppress Cytolysis and IL-2 Production by CD8+ T Cells

“…Suppressor CD8 ϩ T cells have been shown to inhibit both CD4 ϩ and CD8 ϩ T cell effector functions (2,4), although the mechanism of this inhibition is not well defined. Suppressor CD8 ϩ T cells inhibit T cell proliferation and cytotoxicity via contact-dependent mechanisms and/or by using cytokines such as IL-10 (2, 5, 6).…”