Adoptive transfer: the role of perforin in mouse cytotoxic T lymphocyte rejection of human tumor xenografts in vivo

Xenotransplantation. 1998 May;5(2):146-53. doi: 10.1111/j.1399-3089.1998.tb00020.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cytotoxicity, Immunologic
  • Fas Ligand Protein
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / immunology
  • Humans
  • In Vitro Techniques
  • Male
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, SCID
  • Neoplasm Transplantation
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transplantation, Heterologous / immunology*
  • Tumor Cells, Cultured


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin