Failure of anti-T cell monoclonal antibodies to prevent acute tumor allograft rejection is associated with their inability to deplete or inactivate T cells at the site of rejection.
The ability of anti-T cell mAb therapy to prevent acute rejection of a tumor allograft was studied. Injection of both anti-CD4 and anti-CD8 rat Ig2b mAbs 1 day before intraperitoneal implantation of P815 tumor cells into AB6F1 mice prevented tumor rejection in most of the mice. However, injection of the same mAbs on day 8 of tumor growth, i.e., 2 days before the onset of tumor rejection, failed to prevent rapid elimination of P815 cells from the peritoneal cavity. Flow cytometric analysis revealed that whereas splenic T cells remained depleted in these mice for up to 6 days after mAb injection, peritoneal T cells returned to control levels in 4-6 days. Moreover, a significant number of rat IgG+ cells were found in the peritoneal cavity 2 days after mAb administration, thus demonstrating that T cells were not depleted but coated with the mAbs at that time. The antitumor activity of the mAb-coated T cells was not impaired, in that CD8+ peritoneal cells from mice rejecting allogeneic P815 tumor on day 10, and rat IgG+ peritoneal cells taken from mice 2 days after giving them anti-CD8 mAb on day 8, were similarly highly cytotoxic against P815 cells in vitro. Taken together, the results demonstrate that the failure of anti-T cell mAb therapy to prevent the acute rejection of allogeneic P815 tumor was associated with resistance of T cells at the site of rejection to the action of anti-T cell mAbs in vivo.
Rakhmilevich
A L
AL
Trudeau Institute, Saranac Lake, New York 12983.
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal