Prolongation of allograft survival by administration of anti-CD45RB monoclonal antibody is due to alteration of CD45RBhi: CD45RBlo T-cell proportions.
CD45RB monoclonal antibody (mAb) therapy is capable of prolonging allograft survival. We have previously shown that CD45RB mAb enriches the CD45RBlo T-cell population in vitro and in vivo by preferentially depleting CD45RBhi T cells. The present study assessed the importance of CD45RBhi T-cell depletion in murine cardiac allograft survival by infusion of naive CD45RB T-cell subsets. Here we show that naturally occurring CD45RBloCD4+ T cells express regulatory transcription factor Foxp3 and have regulatory function, whereas CD45RBhiCD4+ T cells express low levels of Foxp3 and have effector function. Infusion of syngeneic CD45RBhi T cells significantly reduced graft survival after depletion of CD45RBhi T cells by CD45RB mAb. Reduction of graft survival also occurred when syngeneic CD45RBhi T cells were infused into rapamycin-treated mice, whereas survival was prolonged when CD45RBlo T cells were added. This indicates that an alteration in the balance between regulatory CD45RBlo and effector CD45RBhi T cells is critical to the immunologic function of CD45RB mAb. A strategy to eliminate effector T cells with consequent enrichment of the regulatory T-cell compartment may be an important new strategy in the prevention of rejection.
Luke
P P W
PP
Department of Surgery, The University of Western Ontario, London, Ontario, Canada. patrick.luke@lhsc.on.ca
Deng
J P
JP
Lian
D
D
O'Connell
P J
PJ
Garcia
B
B
Jevnikar
A M
AM
Zhong
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016923:Cell Death; D049109:Cell Proliferation / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D017493:Leukocyte Common Antigens; D020123:Sirolimus