Detecting rejection after mouse Islet transplantation utilizing islet protein-stimulated ELISPOT.
Improved posttransplant monitoring and on-time detection of rejection could improve islet transplantation outcome. The present study explored the possibility of detecting harmful events after mouse islet transplantation measuring the immune responsiveness against islet extracts. Mouse islet transplantations were performed using various donor/recipient combinations, exploring autoimmune (NOD/SCID to NOD, n = 6) and alloimmune events (C57BL/6 to BALB/c, n = 20), a combination of both (C57BL/6 to NOD, n = 8), the absence of both (BALB/c to BALB/c, n = 21), or naive, nontransplanted control mice (n = 14). The immune reactivity was measured by ELISPOT, looking at the ex vivo release of IFN-γ from splenocytes stimulated by islet donor extracts (sonicated islets). The immune reactivity was not altered in the syngeneic and autoimmune models, demonstrating similar levels as nontransplanted controls (p = 0.46 and p = 0.6). Conversely, the occurrence of an allogeneic rejection alone or in combination to autoimmunity was associated to an increase in the level of immune reactivity (p = 0.023 and p = 0.003 vs. respective controls). The observed increase was transient and lost in the postrejection period or after treatment with CTLA4-Ig. Overall, allogeneic rejection was associated to a transient increase in the reactivity of splenocytes against islet proteins. Such a strategy has the potential to improve islet graft monitoring in human and should be further explored.
Transplant Unit, Department of Surgery, University of Geneva Hospitals, Switzerland. Christian.toso@hcuge.ch
Christian
C
Toso
Rena
R
Pawlick
Stéphanie
S
Lacotte
Ryan
R
Edgar
Joy
J
Davis
Michael
M
McCall
Philippe
P
Morel
Gilles
G
Mentha
Thierry
T
Berney
A M James
AM
Shapiro
D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012372:ROC Curve; D013154:Spleen / Q000166:cytology; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D016207:Cytokines; D007166:Immunosuppressive Agents; D007371:Interferon-gamma