CD8+ T cells are capable of rejecting pancreatic islet xenografts.
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.
Yi
S
S
National Pancreas Transplant Unit, University of Sydney at Westmead Hospital, New South Wales, Australia.
Feng
X
X
Hawthorne
W
W
Patel
A
A
Walters
S
S
O'Connell
P J
PJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D053804:Granzymes; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases