SYNERGISTIC IMMUNOSUPPRESSIVE EFFECTS OF MONOCLONAL ANTIBODIES SPECIFIC FOR INTERFERON-GAMMA AND TUMOR NECROSIS FACTOR ALPHA

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Abstract
Interferon gamma and tumor necrosis factor alpha play a significant role in the upregulation of host immunity and inflammation, for example by induction and enhancement of the expression of major histocompatibility complex class I and II antigens on a wide variety of cell types, both in vitro and in vivo. In this study two crossreactive monoclonal antibodies, one specific for human IFN-.gamma. (MD1), the other specific for human TNF-.alpha.(61E71), were tested for immunosuppressive potencies in a skin transplantation study in the rhesus monkey. Treatment with either MD1 or 61E71 alone did not prolong skin-graft-survival times. In combination, however, these antibodies augmented graft survival times significantly. Infiltration of the skin grafts by lymphocytes and histiocytes was delayed, and upregulation of MHC class I and II expression was retarded. This is the first reported demonstration of a synergistic effect of mAbs specific for IFN-.gamma. and TNF-.alpha. in the suppression of allograft rejection in primates.

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