| First Author | Ise W | Year | 2010 |
| Journal | Nat Immunol | Volume | 11 |
| Issue | 2 | Pages | 129-35 |
| PubMed ID | 20037585 | Mgi Jnum | J:158400 |
| Mgi Id | MGI:4438692 | Doi | 10.1038/ni.1835 |
| Citation | Ise W, et al. (2010) CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms. Nat Immunol 11(2):129-35 |
| abstractText | The inhibitory immunoregulatory receptor CTLA-4 is critical in maintaining self-tolerance, but the mechanisms of its actions have remained controversial. Here we examined the antigen specificity of tissue-infiltrating CD4(+) T cells in Ctla4(-/-) mice. After adoptive transfer, T cells isolated from tissues of Ctla4(-/-) mice showed T cell antigen receptor (TCR)-dependent accumulation in the tissues from which they were derived, which suggested reactivity to tissue-specific antigens. We identified the pancreas-specific enzyme PDIA2 as an autoantigen in Ctla4(-/-) mice. CTLA-4 expressed either on PDIA2-specific effector cells or on regulatory T cells was sufficient to control tissue destruction mediated by PDIA2-specific T cells. Our results demonstrate that both cell-intrinsic and non-cell-autonomous actions of CTLA-4 operate to maintain T cell tolerance to a self antigen. |
