Synergistic immunosuppressive effects of monoclonal antibodies specific for interferon-gamma and tumor necrosis factor alpha. A skin transplantation study in the rhesus monkey

Transplantation
H P StevensM Jonker

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.

Citations

Oct 1, 1991·Current Opinion in Immunology·M J Dallman, G J Clark
May 6, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·E BenizriM G Tovey
Nov 15, 1996·Transplantation·P P LeeM R Garovoy
Sep 1, 1994·Transplant Immunology·S MasroorM R First
May 24, 2001·The Journal of Biological Chemistry·P AmelootP Brouckaert

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