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

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Abstract
Monoclonal antibodies specific for human T cell subsets were 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 1 or 2 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 elminated 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. 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. Evidently, 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.