CD8+ T cells are capable of rejecting pancreatic islet xenografts

Transplantation. 2000 Sep 27;70(6):896-906. doi: 10.1097/00007890-200009270-00007.


Background: In this study, the capacity of CD8+ T cells to act as a potential effector mechanism in pancreatic xenograft rejection was examined.

Methods: The fate of pancreatic islet xenografts was studied in mice deficient in MHC class II molecules and CD4+ T cells. Fetal pig pancreas (FPP) or Wistar rat islets (RI) were transplanted into nondiabetic or streptozotocin-induced diabetic I-A knock-out (CII K/O) mice.

Results: CII K/O mice were capable of rejecting both RI and FPP grafts. RI graft survival was not prolonged compared with wild type C57BL/6 controls. However, FPP grafts did survive longer in CII K/O recipients than in C57BL/J6 mice. Both RI and FPP graft rejection were CD8+ T-cell phenomena in CII K/O mice, as anti-CD8 monoclonal antibody prolonged graft survival, there were increased CD8+ T cells in the grafts and spleens of CII K/O recipients, and cell-mediated cytotoxicity was a CD8+ T-cell phenomenon associated with activation of the perforin/granzyme B system. By contrast, RI and FPP graft rejection was a CD4+ T cell-dependent phenomenon in wild type C57BL/6 mice with graft survival prolonged by anti-CD4 monoclonal antibody. There were increased numbers of CD4+ T cells, and cell-mediated cytotoxicity was a CD4+ T-cell phenomenon associated with activation of the Fas/FasL lytic pathway.

Conclusions: The results demonstrate that, in the absence of CD4+ T cells, CD8+ T cells were capable of rejecting both rat and pig pancreatic islet xenografts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / physiology*
  • Cytotoxicity, Immunologic
  • Flow Cytometry
  • Granzymes
  • Islets of Langerhans Transplantation / immunology*
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Rats
  • Rats, Wistar
  • Serine Endopeptidases / biosynthesis
  • Spleen / cytology
  • Swine
  • T-Lymphocytes, Cytotoxic / metabolism
  • Transplantation, Heterologous / immunology*
  • Transplantation, Heterologous / pathology


  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Granzymes
  • Gzmb protein, mouse
  • Gzmb protein, rat
  • Serine Endopeptidases