*Purpose: Current clinical practice of intestinal transplantation is limited due to a high rate of graft failure and patient mortality. In the present study, we sought to develope a murine single major histocompatibility complex (MHC) mismatched (B6-K^dàB6) paratopic intestinal transplantation model, in order to elucidate the role of alloimmune responses in allograft rejection in absence of GVHD.

*Methods: A full-length donor jejunum either from C57BL6 (B6) or B6-K^d was transplanted to B6 recipients. The proximal part of the donor jejunum was anastomosed to ileum, while the distal end is exteriorized as an ostomy (paratopic transplant). Syngeneic and allogeneic transplant recipients were sacrificed at different time points for histologic and flow cytometric analysis. Some syngeneic transplant recipients were used to obtain intestinal autograft biopsies by endoscopy through ostomy on day 15 post-transplant.

*Results: We observed that B6àB6 syngeneic transplant recipients survived up to two months post-transplant without any physical impairment and/or weight loss, establishing the feasibility of murine paratopic intestinal transplant model. Histologic evaluation of intestinal autograft biopsies collected on day 15 post-transplant demonstrated completely normal crypts and villi. Similarly, whole autografts retrieved on day 28 post-transplant also showed normal crypts and villi, scattered CD3 T cells, and absence of apoptotic cryptic cells. In contrast, B6-K^d intestinal allografts retrieved on day 7 post-transplant showed focal cryptic destruction with villous blunting, moderate to severe CD3 T cell infiltration, and apoptotic cryptic cells, suggesting ongoing rejection processes. Flow cytometric analysis of immune cells showed increased numbers of CD11c⁺CD11b^–CD103⁺ DCs with elevated expression of MHC II dendritic cells in allografts in comparison to autografts. We did not observe any sign of GVHD in this model.

*Conclusions: Our data demonstrate that we successfully developed a mouse model of paratopic intestinal transplant model. We show that CD11c⁺CD11b^–CD103⁺ dendritic cells are associated with intestinal allograft rejection. Further studies utilizing this model will allow us to precisely define alloimmune responses underlying intestinal allograft rejection.

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