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Detecting rejection after mouse Islet transplantation utilizing islet protein-stimulated ELISPOT.

Pawlick, Rena
Edgar, Ryan
Davis, Joy
McCall, Michael
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Published in Cell transplantation. 2011, vol. 20, no. 6, p. 955-62
Abstract 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.
Keywords AnimalsAutoimmunity/physiologyCytokines/metabolismDiabetes Mellitus, Experimental/therapyDisease Models, AnimalEnzyme-Linked Immunospot AssayFemaleGraft Rejection/immunologyImmunosuppressive Agents/pharmacologyInterferon-gamma/metabolismIslets of Langerhans Transplantation/immunologyMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODROC CurveSpleen/cytologyTransplantation, AutologousTransplantation, Homologous
PMID: 21054945
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Research groups Hépatologie chirurgicale (327)
La transplantation d'îlots de Langerhans (623)
Transplantation et hépatologie (905)
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TOSO, Christian et al. Detecting rejection after mouse Islet transplantation utilizing islet protein-stimulated ELISPOT. In: Cell transplantation, 2011, vol. 20, n° 6, p. 955-62. doi: 10.3727/096368910X539137 https://archive-ouverte.unige.ch/unige:24880

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Deposited on : 2013-01-02

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