Islet transplantation in the discordant tilapia-to- XXXX model: a novel application of alginate microencapsulation in the study of xenograft rejection.

@entity59 @entity19 @entity5168 @entity3839 @entity61 @entity1961 @entity3440 @entity19160 @entity630
BACKGROUND: Tilapia islet xenograft rejection is characterized by infiltration with macrophages (Mphis), eosinophils (Ephis), and T lymphocytes. The presence of these cells indicates they contribute to rejection; therefore, an attempt was made to assess their role through host immunomodulation. METHODS: Tilapia islet cells were transplanted under the kidney capsule of @entity3839 diabetic Balb/c @entity19 , which were then treated with one of several immunomodulatory regimes targeting Mphis, Ephis, or T cells. Mphis were depleted using either @entity3440 or liposome-entrapped @entity19160 . Ephi migration was blocked using monoclonal antibodies (mAbs) targeting interleukin (IL)-4 or @entity59 . T-cell function was altered with mAbs targeting @entity5168 , @entity1961 , or CD8. Finally, T helper (Th)1 and @entity61 activity was altered by depleting essential @entity630 or @entity61 cytokines with mAbs or by promoting a @entity630 response with the injection of exogenous IL-12. The effects of antibody-mediated immunomodulation on graft survival were initially screened by cotransplanting alginate-encapsulated, mAb-secreting hybridoma cells into the peritoneal cavity at the time of islet transplantation. Significant prolongation was then confirmed using purified antibodies injected at the time of islet transplantation. Rejected grafts were examined histologically, and immunohistochemistry was used to assess the cellular infiltrates for each of the treatment groups. RESULTS: Modulation of Mphis and Ephis alone did not significantly delay functional rejection of tilapia islet grafts (maximal mean graft survival time [mGST]=7.1+/-1.7 and 9.4+/-3.4, respectively) compared with untreated controls (mGST=8.2+/-1.0). Treatment of transplanted animals with antibodies against @entity5168 or @entity1961 significantly promoted graft survival (maximal mGST=16.3+/-5.8 and 34.0+/-11.6, respectively), whereas targeting CD8 and @entity630 and @entity61 cytokines showed no prolonging effect (maximal mGST=7.8+/-2.9 and 9.5+/-4.3, respectively). CONCLUSION: Our results indicate that rejection in the tilapia-to- @entity19 model follows a pattern similar to other models of discordant islet cell xenotransplantation.
