Phenotypic and functional characteristic of a newly identified CD8 ⁺Foxp3^-CD103⁺ regulatory T cells

TGF-β and Foxp3 expressions are crucial for the induction and functional activity of CD4⁺Foxp3⁺ regulatory T (iTreg) cells. Here, we demonstrate that although TGF-β-primed CD8⁺ cells display much lower Foxp3 expression, their suppressive capacity is equivalent to that of CD4⁺ iTreg cells, and both Foxp3^- and Foxp3⁺ CD8+ subsets have suppressive activities in vitro and in vivo. CD8⁺Foxp3^- iTreg cells produce little IFN-γ but almost no IL-2, and display a typical anergic phenotype. Among phenotypic markers expressed in CD8⁺Foxp3^- cells, we identify CD103 expression particularly crucial for the generation and function of this subset. Moreover, IL-10 and TGF-β signals rather than cytotoxicity mediate the suppressive effect of this novel Treg population. Therefore, TGF-β can induce both CD8⁺Foxp3^- and CD8⁺Foxp3 ⁺ iTreg subsets, which may represent the unique immunoregulatory means to treat autoimmune and inflammatory diseases.