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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4475-4483.
Prepublished online as a Blood First Edition Paper on February 7, 2006; DOI 10.1182/blood-2005-10-3994.
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IMMUNOBIOLOGY
Cytokine-induced IL-10–secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage
Alistair Noble,
Angela Giorgini, and
Jamie A. Leggat
From the Medical Research Council (MRC) and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, United Kingdom.
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.
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