ADOPTIVE TRANSFER - THE ROLE OF PERFORIN IN MOUSE CYTOTOXIC T-LYMPHOCYTE REJECTION OF HUMAN TUMOR XENOGRAFTS IN-VIVO

The popliteal lymph node cells of immunocompetent mice generated a str ong in vitro cytotoxic response to footpad injection of several human tumor cell lines and the resulting mouse effector cells predominantly used a perforin-mediated cytotoxic mechanism. A relatively minor Fast- dependent cytotoxic response to CEM-CCRF and Jurkat leukemias, but not colon carcinoma COLO 205 cells, was also detected in immunized perfor in-deficient mice. In vitro depletion of CD3(+) CD8(+) T cells, but no t CD4(+) T or NK1.1(+) cells, completely inhibited lysis of human tumo r cells, suggesting that CD3(+) CD8(+) T cells were effecters of perfo rin-mediated xenospecific cytotoxicity. Xenospecific cytotoxic T cells from wild-type mice were extremely efficient at rejecting tumor when adoptively transferred into scid mice bearing established COLO 205, CE M-CCRF or Jurkat tumor xenografts. By contrast, cytotoxic T lymphocyte s of perforin-deficient mice had no effect on the growth of establishe d tumor xenografts. These data indicate that perforin, and hence direc t cytotoxicity, plays a key role in the ability of adoptively transfer red CD8(+) cytotoxic T lymphocytes to eradicate established xenografts .