| First Author | Fu T | Year | 2011 |
| Journal | Mol Immunol | Volume | 48 |
| Issue | 5 | Pages | 751-9 |
| PubMed ID | 21168915 | Mgi Jnum | J:168475 |
| Mgi Id | MGI:4888432 | Doi | 10.1016/j.molimm.2010.11.016 |
| Citation | Fu T, et al. (2011) Accelerated acute allograft rejection accompanied by enhanced T-cell proliferation and attenuated Treg function in RBP-J deficient mice. Mol Immunol 48(5):751-9 |
| abstractText | Acute allograft rejection (AAR) involves both the innate and the adaptive immune systems. As a critical pathway in peripheral T-cell differentiation and function, Notch signaling is potentially involved in the modulation of AAR, but its role in alloimmune responses has not been fully addressed. By using fully MHC-mismatched allograft transplantation model and T-cell specific RBP-J deficient mice, we examined the role of Notch/RBP-J pathway in alloimmune responses in vivo. AAR was significantly accelerated in RBP-J deficient mice compared with the wild-type controls, as demonstrated by the marked reduction in graft survival. The reduction in graft survival was associated with augmented alloantigen specific T-cell proliferation and increased number of Th1, Th2, and Th17 cells in the RBP-J deficient recipient mice. Furthermore, although the frequency of CD4(+)CD25(+)Foxp3(+) Tregs was intact in RBP-J knockout recipients, their ability to suppress Teff responses in vitro was significantly dampened. These findings suggest that Notch/RBP-J pathway may attenuate AAR by suppressing in vivo expansion of alloreactive T-cell proliferation and facilitating CD4(+)CD25(+) Treg suppression ability, indicating that Notch pathway could be exploited to limit T-cell-mediated AAR. |
