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.

Subcutaneous inverse vaccination with PLGA particles loaded with a MOG peptide and IL-10 decreases the severity of experimental autoimmune encephalomyelitis

“…Our data do not support the possibility that the protective effect was mediated by CD4 + CD25 + FoxP3 + T REG cells since their numbers were similar in the spleens of mice treated with blank-PLGA and those treated with IL-10-PLGA plus MOG-PLGA (data not shown). This is in line with other reports [34], but it does not rule out the involvement of other populations of regulatory cells or CD4 + CD25 + FoxP3 + T REG cells compartimentalized in other tissues [36,37].…”

Long term effect of gut microbiota transfer on diabetes development

“…Antigen-presenting cells within the gut are directly affected [38], with recent evidence suggesting that particular metabolites such as short-chain fatty acids are key players [39, 40]. We have shown that the mice transferred with the MyD88−/−NOD microbiota expressed regulatory immune responses in the gut, with increased IgA and TGFβ as well as a considerable increase in a population of CD8 + CD103 + T cells which have been identified to be a regulatory CD8 population [41]. It is not clear which cells produce the increased TGFβ, but recent evidence suggests that TGFβ is important for upregulation of CD103 and necessary for the maintenance of T resident memory cells of the gut [42].…”

Increased proportion of FoxP3+ regulatory T cells in tumor infiltrating lymphocytes is associated with tumor recurrence and reduced survival in patients with glioblastoma

“…While increased FoxP3 expressing Treg ratios may be a poor predictor for survival, other immunosuppressive populations of cells such as CD8+ FoxP3− CD103+ T cells, myeloid-derived suppressor cells and M2 macrophages may contribute to clinical outcomes in patients with GBM and more comprehensive analysis of the ratio of non-regulatory to regulatory populations of leukocytes is requisite [35–37]. Since Foxp3 is not an exhaustive marker of Tregs, and FoxP3 expressing T cells may have a more ubiquitous role than previously understood, additional analysis of Treg phenotype and function may prove informative [38–41].…”