Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage.
Populations of regulatory T cells (Tregs) control autoimmune and allergic immunopathology induced by self or foreign antigens. Several types of CD4(+) MHC class II-restricted Treg populations have been characterized, but the biology of CD8(+), MHC class I-restricted Tregs is less understood. We show here that CD8(+) Tregs are rapidly generated in the presence of IL-4 and IL-12, produce IL-10, and exhibit a unique cell-surface phenotype with coexpression of activation and naive cell-associated markers. They block activation of naive or effector T cells and suppress IgG/IgE antibody responses and graft-versus-host disease in vivo. Suppression is dependent on cell contact and mediated by direct T-cell-T-cell interaction that antagonizes T-cell-receptor (TCR) signals. The data establish the existence of a CD8 T-cell suppressor effector subset distinct in both phenotype and function from T cytotoxic 1 (Tc1) and Tc2 cells. Production of such CD8 Tregs has potential for cell-based therapy of CD4 or CD8 T-cell-mediated disease.
Noble
Alistair
A
Medical Research Council, King's College London, UK. alistair.noble@kcl.ac.uk
Giorgini
Angela
A
Leggat
Jamie A
JA
D019264:Adoptive Transfer; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D002450:Cell Communication / Q000276:immunology; D019070:Cell Lineage; D016207:Cytokines / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation
D000954:Antigens, Surface; D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4