title: Anti-CD4 monoclonal antibody effects cellular hyporesponsiveness and prolongs renal allograft survival in the rat.
abstract: 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.
authors.affiliation: Department of Medicine, Harvard Center for the Study of Kidney Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: M H
authors.initials: MH
authors.lastname: Sayegh
authors.forename: J P
authors.initials: JP
authors.lastname: Kut
authors.forename: E L
authors.initials: EL
authors.lastname: Milford
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D010835:Phytohemagglutinins