title: Accelerated acute allograft rejection accompanied by enhanced T-cell proliferation and attenuated Treg function in RBP-J deficient mice.
abstract: 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.
authors.affiliation: Xijing Hospital for Digestive Disease, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Fu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Gang
authors.initials: G
authors.lastname: Ji
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Zheng
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Chen
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D000208:Acute Disease; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch