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

Abstract

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. © 2013 The Author.