| First Author | Tong H | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 3 | Pages | e0195119 |
| PubMed ID | 29596528 | Mgi Jnum | J:261070 |
| Mgi Id | MGI:6151019 | Doi | 10.1371/journal.pone.0195119 |
| Citation | Tong H, et al. (2018) Apaf1 plays a negative regulatory role in T cell responses by suppressing activation of antigen-stimulated T cells. PLoS One 13(3):e0195119 |
| abstractText | Apaf1 is a critical component of the apoptosome and initiates apoptosis downstream mitochondrial damages. Although the importance of Apaf1 in embryonic development was shown, the role of Apaf1 in immune responses, especially T cell responses, has yet to be elucidated. We generated T cell-specific Apaf1-deficient mice (Lck-Cre-Apaf1f/f mice) and examined the antigen-specific delayed-type hypersensitivity (DTH). Lck-Cre-Apaf1f/f mice exhibited exacerbation of DTH responses as compared with Apaf1-sufficient control mice. In Lck-Cre-Apaf1f/f mice, antigen-specific T cells proliferated more, and produced more inflammatory cytokines than control T cells. Apaf1-deficient T cells from antigen-immunized mice showed higher percentages of activation phenotypes upon restimulation in vitro. Apaf1-deficient T cells from naive (non-immunized) mice also showed higher proliferation activity and cytokine production over control cells. The impact of Apaf1-deficiency in T cells, however, was not restored by a pan-caspase inhibitor, suggesting that the role of Apaf1 in T cell responses was caspase-independent/non-apoptotic. These data collectively demonstrated that Apaf1 is a negative regulator of T cell responses and implicated Apaf1 as a potential target for immunosuppressive drug discovery. |
