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Adoptive transfer: The role of perforin in mouse cytotoxic T lymphocyte rejection of human tumor xenografts in vivo
Author(s) -
Smyth Mark J.,
Kershaw Michael H.,
Darcy Phillip K.,
Trapani Joseph A.
Publication year - 1998
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.1998.tb00020.x
Subject(s) - cytotoxic t cell , perforin , adoptive cell transfer , in vivo , immunology , transplantation , cancer research , biology , medicine , in vitro , genetics , surgery
The popliteal lymph node cells of immunocompetent mice generated a strong 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 FasL‐dependent cytotoxic response to CEM‐CCRF and Jurkat leukemias, but not colon carcinoma COLO 205 cells, was also detected in immunized perforin‐deficient mice. In vitro depletion of CD3 + CD8 + T cells, but not CD4 + T or NK1.1 + cells, completely inhibited lysis of human tumor cells, suggesting that CD3 + CD8 + T cells were effectors of perforin‐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, CEM‐CCRF, or Jurkat tumor xenografts. By contrast, cytotoxic T lymphocytes of perforin‐deficient mice had no effect on the growth of established tumor xenografts. These data indicate that perforin, and hence direct cytotoxicity, plays a key role in the ability of adoptively transferred CD8 + cytotoxic T lymphocytes to eradicate established xenografts.