Inhibition of allospecific response in pancreatic islet transplantation: the glycan approach.
Host resistance has precluded clinical islet transplantation from becoming a consistent therapy for type I diabetic patients, mainly due to both specific and nonspecific processes. O-glycosylated proteins have a primary role in immunologic synapses. Therefore, we investigated the effects of a putative immunomodulatory effect of the cleavage of these molecules on islet allotransplantation.


METHODS
Murine islets were treated with O-sialoglycoprotein endopeptidase. Three endpoints were studied: (1) proliferation in allogeneic mixed islet mononuclear cell reactions using treated and control irradiated islets as stimulator cells of mononuclear cells; (2) expression of IA-d on monocytes using 48-hour transplants of treated versus control mouse islets into subcutaneous capsules; (3) posttransplant graft function in an in vivo model of islet allotransplantation. Treated and control islets were transplanted in diabetic mice treated daily with cyclosporine. Glycemia was monitored to determine diabetes reversion.


RESULTS
The allogeneic proliferative response was maximal when allogeneic mononuclear cells were mixed with control islets; it was significantly decreased with treated islets. Mean proliferative inhibition rate of treated vs. control was 62%. IA-d expression on monocytes was maximal in control islets. Reversion was significantly different for treated versus control islets with its duration varied from 3 to 7 days.


CONCLUSIONS
These results suggest that treatment of islets with O-sialoglycoprotein endopeptidase may modulate allogeneic immunologic reactions.
Vieiro
M
M
Instituto de Ciencias Básicas y Medicina Experimental del Hospital Italiano de Bs As, Buenos Aires, Argentina.
Ceballos
C
C
Barrionuevo
P
P
Hyon
S H
SH
Isturiz
M
M
Argibay
P
P
D000818:Animals; D002455:Cell Division; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D006031:Glycosylation; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008666:Metalloendopeptidases / Q000494:pharmacology*; D051379:Mice; D014184:Transplantation, Homologous / Q000502:physiology
D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase