CD28/B7-mediated costimulation is required for parathyroid gland allograft rejection in rats.
The activation of T cells to differentiate and to proliferate is an essential step in the immune response to antigen, especially in cell mediated acute allograft rejection. Besides the interaction of CD3/TCR complex with Ag/MHC complex presented on antigen-presenting cells, a complete T-cell activation and proliferation requires a second costimulatory signal. The interaction of CD28/CTLA-4 and B7 is a major costimulatory pathway for T Cell activation. Inhibition of this pathway results in development of antigen-specific unresponsiveness and clonal anergy. In present study, the biologic function of anti-CD28 monoclonal antibody and its Fab fragment were investigated in vitro and in vivo. The results indicate that mAbCD28 and its Fab fragments could promote the functional recovery of allografts and prolong the graft survival, but could not reverse the acute rejection or induce transplantation tolerance in the rat PTG allograft model. We also found that peripheral TNF-alpha level and NK-cell activity were suppressed in the presence of mAbCD28 and its Fab fragments for a relatively long time after PTG transplantation.
Xiao
Y
Y
Department of General Surgery, Peking Union Medical College Hospital, Beijing 100730.
Zhu
Y
Y
Chen
L
L
Wang
S
S
He
X
X
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D006084:Graft Rejection / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010280:Parathyroid Glands / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction; D014181:Transplantation Immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; C556708:Ctla4 protein, rat; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha