| First Author | Waickman AT | Year | 2017 |
| Journal | Cytokine | Volume | 99 |
| Pages | 266-274 | PubMed ID | 28807496 |
| Mgi Jnum | J:326000 | Mgi Id | MGI:6878505 |
| Doi | 10.1016/j.cyto.2017.08.004 | Citation | Waickman AT, et al. (2017) CD4 effector T cell differentiation is controlled by IL-15 that is expressed and presented in trans. Cytokine 99:266-274 |
| abstractText | T cells are both producers and consumers of cytokines, and autocrine cytokine signaling plays a critical role in T cell immunity. IL-15 is a homeostatic cytokine for T cells that also controls inflammatory immune responses. An autocrine role of T cell-derived IL-15, however, remains unclear. Here we examined IL-15 expression and signaling upon effector T cell differentiation in mice, and, surprisingly, found that CD4 T cells did not express IL-15. CD4 T cells lacked Il15 gene reporter activity, did not contain IL-15 transcripts, and did not produce IL-15Ralpha, the proprietary IL-15 receptor required for IL-15 trans-presentation. Moreover, IL-15 failed to inhibit Th17 cell differentiation and failed to generate Foxp3(+) Treg cells in vitro. IL-2, which utilizes the same IL-2Rbeta/gammac receptor complex, however, successfully did so. Exogenous IL-15 only exerted bioactivity and controlled T cell differentiation when it was trans-presented by IL-15Ralpha. Consequently, IL-15Ralpha-bound IL-15, but not free IL-15, suppressed Th17 cell differentiation and induced Treg cell generation. Collectively, these results reveal the absence of an IL-15 autocrine loop in CD4 T cells and strongly suggest that IL-15 trans-presentation by non-CD4 T cells is the primary mechanism via which IL-15 controls CD4 effector T cell differentiation. |
