Anti-CD4 monoclonal antibody effects cellular hyporesponsiveness and prolongs renal allograft survival in the rat.
LEW strain rats received BN strain renal allografts and were treated with daily injections of 100 micrograms BWH-4, a new IgG2a mouse anti-rat CD4 monoclonal antibody, intravenously for 5 to 10 days. These animals had a median actuarial survival of 28 days. Control animals rejected their grafts and died of uremia between day 6 and 8 post transplant. Animals treated with BWH-4 did not suffer acute graft loss and had stable renal function throughout the follow-up period of 5 weeks. Peripheral blood, lymph node, and splenic lymphocytes showed 60-80% decrease in the CD4+ subset which normalized by 4 weeks after transplantation. There was depressed proliferative response of lymph node cells to alloantigen and mitogen which persisted up to 4 weeks after cessation of therapy. Treated animals produced anti-BN antibodies as well as antibodies to the infused BWH-4. There was no correlation, however, between these humoral responses and allograft function. We conclude that low-dose monotherapy with the BWH-4 anti-CD4 monoclonal antibody effects cellular hyporesponsiveness, prevents acute renal allograft rejection, and prolongs survival.
Sayegh
M H
MH
Department of Medicine, Harvard Center for the Study of Kidney Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Kut
J P
JP
Milford
E L
EL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000917:Antibody Formation / Q000187:drug effects; D015704:CD4 Antigens / Q000276:immunology*; D006085:Graft Survival / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D010835:Phytohemagglutinins