Anti-HLA class I antibodies activate endothelial cells and promote chronic rejection.
Transplant recipients exhibiting a humoral immune response to the allograft demonstrate lower graft survival and increased risk for the development of chronic rejection and transplant arteriosclerosis. Our studies suggest that anti-HLA class I antibodies (Ab) play an important role in controlling endothelial cell (EC) function by binding to class I molecules on the surface of the EC and transducing intracellular signals. Anti-HLA Ab exhibit two primary effector functions: stimulation of cell proliferation and up-regulation of cell survival genes. Importantly, the intracellular events initiated by class I ligation appear to be influenced by the concentration of the Ab. High-titered anti-HLA Ab stimulate cell proliferation whereas low-titered Ab activate the PI3K/Akt pathway and promote expression of cell survival proteins including Bcl-2 and Bcl-xL. Anti-HLA class I Ab may contribute to the process of chronic allograft rejection by promoting EC survival and proliferation.
Jin
Yi-Ping
YP
Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Jindra
Peter T
PT
Gong
Ke Wei
KW
Lepin
Eric J
EJ
Reed
Elaine F
EF
D000818:Animals; D004730:Endothelium, Vascular / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D015398:Signal Transduction
D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies