Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts.
Binding of CD95 (Fas/APO-1) by its ligand (CD95L) commonly induces apoptosis. Apoptosis of activated T cells, induced by CD95L expressed in the rodent testis, has been proposed to be the mechanism of immune privilege [Bellgrau, D., Gold, D., Selawry, H., Moore, J., Franzusoff, A. & Duke, R. C. (1995) Nature (London) 377, 630-632]. To test whether CD95L could protect pancreatic islet grafts from rejection, we made transgenic mice expressing murine CD95L on their islet beta cells and transplanted fetal pancreata under the kidney capsules of allogeneic animals. Expression of CD95L failed to protect the grafts from rejection. However, transgenic mice developed a granulocytic infiltration in their pancreata. These results demonstrate a pro-inflammatory function of CD95L and suggest that expression of CD95L may not be sufficient to protect organ allografts.
Allison
J
J
The Walter and Eliza Hall Institute for Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia. Allison@WEHI.EDU.AU
Georgiou
H M
HM
Strasser
A
A
Vaux
D L
DL
D000818:Animals; D002465:Cell Movement; D053222:Fas Ligand Protein; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006085:Graft Survival / Q000276:immunology*; D006098:Granulocytes / Q000276:immunology* / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D014184:Transplantation, Homologous
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins