Synergistic immunosuppressive effects of monoclonal antibodies specific for interferon-gamma and tumor necrosis factor alpha. A skin transplantation study in the rhesus monkey.
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.
Stevens
H P
HP
Department of Plastic and Reconstructive Surgery, University Hospital, Dijkzigt, Rotterdam, The Netherlands.
van der Kwast
T H
TH
van der Meide
P H
PH
Vuzevski
V D
VD
Buurman
W A
WA
Jonker
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology*; D006085:Graft Survival / Q000276:immunology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008253:Macaca mulatta; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma