Prevention and reversal of renal allograft rejection by antibody against CD45RB.
Rejection continues to be the single largest impediment to successful organ transplantation. Antilymphocyte globulin, which contains antibodies that react with the leukocyte common antigen known as CD45, has proved to be one of the most effective agents for preventing rejection. We have shown earlier that a monoclonal antibody directed against the RB isoform of CD45 substantially inhibits the alloreactivity of human CD4+ lymphocytes in vitro. Here we investigate whether CD45RB could be an appropriate target for preventing renal allograft rejection in mice. Mice treated with two injections of a monoclonal antibody (MB23G2) raised against CD45RB protein all survived and had normal renal function. Furthermore, this antibody reversed acute rejection when therapy was delayed until day 4, and the mice survived for their natural lifespan. The immunosuppression achieved may find application in the prevention and treatment of transplant rejection in man.
Lazarovits
A I
AI
John P. Robarts Research Institute, Multi-Organ Transplant Service, London Health Sciences Centre, University Campus, University of Western Ontario, London, Ontario, Canada.
Poppema
S
S
Zhang
Z
Z
Khandaker
M
M
Le Feuvre
C E
CE
Singhal
S K
SK
Garcia
B M
BM
Ogasa
N
N
Jevnikar
A M
AM
White
M H
MH
Singh
G
G
Stiller
C R
CR
Zhong
R Z
RZ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051381:Rats; D016038:Skin Transplantation / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D014443:Tyrosine; D003404:Creatinine; D017493:Leukocyte Common Antigens