The effects of OKT4A monoclonal antibody on cellular immunity of nonhuman primate renal allograft recipients.
Significant differences in cellular responses were found among allograft recipients treated with various OKT4A mAb protocols. Recipients of multiple infusion low-dose and 2-bolus OKT4A immunosuppressive regimens regularly showed potent donor-specific cytotoxic CD8+ and CD4+ intragraft T cells and donor-reactive PBMC in MLC tests. In contrast, PBMC isolated from recipients of high-dose OKT4A therapy generally showed very weak or no response to donor-antigens during the later posttransplant periods. Furthermore, an absence of IL2-responsive intragraft cells was found to correlate with stable graft function in these recipients. We conclude that OKT4A mAb, in high doses, can block allosensitization and induce donor-specific nonresponsiveness in vivo. An OKT4A-based therapy, therefore, may have the potential of inducing long-lasting donor-specific immunosuppression, or even tolerance.
Wee
S L
SL
Transplantation Unit, Massachusetts General Hospital, Boston 02214.
Stroka
D M
DM
Preffer
F I
FI
Jolliffe
L K
LK
Colvin
R B
RB
Cosimi
A B
AB
D000818:Animals; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002465:Cell Movement; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000592:standards; D007376:Interleukin-2 / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D007376:Interleukin-2