Autoreactive human peripheral blood CD8+ T cells with a regulatory phenotype and function.
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.
Jarvis
Lorna B
LB
University of Cambridge Clinical School, Dept. of Medicine, Addenbrooke's Hospital, Cambridge, UK.
Matyszak
Malgosia K
MK
Duggleby
Richard C
RC
Goodall
Jane C
JC
Hall
Frances C
FC
Gaston
J S Hill
JS
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556708:Ctla4 protein, rat; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2