Detecting Rejection after Mouse Islet Transplantation Utilizing Islet Protein-Stimulated ELISPOT

Cell Transplantation

Article

Joy Davis¹  Ryan Edgar¹  A. M. James Shapiro¹  Rena Pawlick¹  Michael McCall¹  Thierry Berney²  Philippe Morel²  Stéphanie Lacotte²  Christian Toso²  Gilles Mentha² 

[1] Section of Hepatobiliary, Pancreatic and Transplant Surgery, University of Alberta, Edmonton, Canada;Transplant Unit, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland;

关键词: Monitoring;    Diabetes;    Islets;    Transplantation;    Cytokine;   

DOI  :  10.3727/096368910X539137

 received in 2010-05-13, accepted in 2010-10-19,  发布年份 2011

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2011 Cognizant Comm. Corp.

【 图 表 】

Figure 2

Figure 4.

Figure 3.

Figure 1.