EFFECTS OF IN VITRO AND IN VIVO ANTICANINE T LYMPHOCYTE AND ANTICANINE CLASS II-SPECIFIC MONOCLONAL ANTIBODIES IN THE BEAGLE

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Abstract
Two murine anticanine lymphocyte monoclonal antibodies, designated T83 and B1F6, were assessed for (1) in vitro antiepitope activity to circulating lymphocyte subsets, their functional effects on lymphoproliferative assays and binding specificities to diverse cell suspensions and tissue sections; (2) in vivo effects after administration on cells expressing the target epitopes, lymphoproliferation, and allograft survival; and (3) the host immune response to the injected murine immunoglobulins. The monoclonal antibody T83 (IgG3) appeared to be specific for a T cell subset with an up-regulating function on lymphoproliferation. It caused a profound depletion of cells with the appropriate epitope after intravenous administration but it bound to lymphocyte membrane epitopes on some cells in peripheral blood that did not become depleted and putatively caused other modulating effects on lymphocyte function. The monoclonal antibody B1F6 (IgG2a, previously described) was immunologically specific in vitro for cells expressing class II major histocompatibility complex antigens. In the dog, this also consisted of 50% of T lymphocytes. After intravenous administration, there were functional effects similar to those of T83. A modest prolongation of survival of renal allografts was observed when both mAbs were used as the sole immunosuppressive agent. These studies also demonstrated the occurrence of natural canine antimurine IgG antibodies. Administration of either monoclonal antibody was followed by a rapid increase in the concentration of the antimouse antibody(s). We postulate that the presence of canine natural antimouse IgG markedly influenced the biologic effects of in vivo administered monoclonals.