EFFECTS OF IN VIVO ADMINISTRATION OF MONOCLONAL ANTIBODIES... : Transplantation (original) (raw)

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EFFECTS OF IN VIVO ADMINISTRATION OF MONOCLONAL ANTIBODIES SPECIFIC FOR HUMAN T CELL SUBPOPULATIONS ON THE IMMUNE SYSTEM IN A RHESUS MONKEY MODEL

Primate Center TNO, 2288 GJ Rijswijk, The Netherlands; and Ortho Pharmaceutical Corp., Division of Immunobiology, Raritan, New Jersey 08869

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Abstract

Monoclonal antibodies specific for human T cell subsets have been tested for their immunosuppressive effect in a rhesus monkey skin graft model. Rhesus monkeys were injected i.v. daily with antibodies specific for helper T cells (OKT4 and 4A), for cytotoxic/suppressor T cells (OKT8A), or all peripheral T cells (OKT11A), and they received an allogeneic skin graft one or two days after the initial antibody treatment. The OKT4, 4A, and 11A antibodies prolonged skin graft survival, but OKT8A did not. All animals were carefully monitored regarding levels of T cell subsets and antibody formation to the injected monoclonal antibody. The relevant T cell subset was not eliminated from the circulation when OKT4 and OKT4A antibodies were given separately. The OKT4+ cells remained in the circulation coated with antibody. OKT4+ cells could no longer be demonstrated when both OKT4 and 4A were given simultaneously. However, this difference in effect on the OKT4+ cells did not influence skin graft survival time. All animals receiving monoclonal antibody treatment developed antimouse-Ig antibodies after 10 to 13 days of treatment, which presumably counteracted the effect of the antibodies. From these data it appears that the rhesus monkey is a useful animal model in which to investigate the potential of monoclonal antibodies against human lymphocyte subpopulations to modify and regulate the immune response in an orderly fashion.