| First Author | Burrell BE | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 6 | Pages | 3906-14 |
| PubMed ID | 18768845 | Mgi Jnum | J:139106 |
| Mgi Id | MGI:3807328 | Doi | 10.4049/jimmunol.181.6.3906 |
| Citation | Burrell BE, et al. (2008) CD8+ Th17 mediate costimulation blockade-resistant allograft rejection in T-bet-deficient mice. J Immunol 181(6):3906-14 |
| abstractText | While studying Th responses induced by cardiac transplantation, we observed that mice deficient in the Th1 transcription factor T-bet (T-bet(-/-)) mount both Th1 and Th17 responses, whereas wild-type recipients mount only Th1 responses. Cells producing both IFN-gamma and IL-17 were readily detectable within the rejecting graft of T-bet(-/-) recipients, but were absent from the spleen, indicating that the in vivo microenvironment influences Th function. In addition, disrupting CD40-CD40L costimulatory interactions was highly effective at prolonging allograft survival in WT mice, but ineffective in T-bet(-/-) recipients. In this study, we report that CD8(+) Th17 mediate costimulation blockade-resistant rejection in T-bet(-/-) allograft recipients. Depleting CD8(+) cells or neutralizing IL-17 or the Th17-inducing cytokine IL-6 ablated the Th17 response and reversed costimulation blockade-resistant graft rejection. Neutralizing IL-4 in IFN-gamma(-/-) allograft recipients did not induce Th17, suggesting that T-bet, rather than IL-4 and IFN-gamma (known inhibitors of Th17), plays a critical role in negatively regulating Th17 in the transplant setting. |
