CD11c+CD8+ T cells: two-faced adaptive immune regulators

Regulatory cells, important controllers of immune homeostasis, carry out a multi-pronged attack by deleting overactive pathogenic immune cells, by supporting anergy, and by blocking effector functions, thereby contributing to the amelioration of disease. CD8+ T cells co-expressing CD11c are a new addition to the growing list of regulatory cells. Naïve mice harbor CD11c-expressing CD8+ T cells (<3%) that expand further in an antigen-dependent manner. Although activated CD11c+CD8+ T cells express suppressive cytokines such as IL-10 and TGF-beta, their production of IFN-gamma is central to their immune suppressive potential. The CD11c+CD8+ T cells target pathogenic CD4+ T cells in a cell-cell contact dependent manner via IDO- and GCN2-dependent mechanisms. Adoptive transfer of activated CD11c+CD8+ T cells halts the progression of autoimmune rheumatoid arthritis and colitis. However, in certain virus and cancer models the CD11c+CD8+ T cells assume the role of immune effectors, boosting immune potential. This seemingly dual nature of these cells--exerting regulatory vs. effector activities--makes them an attractive therapeutic target. In this review, we discuss the discovery, origins and developmental requirements of CD11c+CD8+cells, and the basis of their immuno-suppressive and effector potentials.