Characterization of an Experimental Model of Allogeneic Heterotopic Intestinal Transplantation in Rats

IVANA IVANOFF MARINOFF; RODRIGO PAPA-GOBBI; VECCHIO DEZILLIO, LEANDRO EMMANUEL; LAUSADA NATALIA; MACHUCA MARIANA; PABLO STRINGA; MARTÍN RUMBO

Mar Del Plata

Congreso; Reunión Anual de Sociedades de Biociencias SAI-SAIC-SAFIS 2022; 2022

SAI - SAFIS - SAIC

Graft rejection is one of the most common complications associated with intestinal transplantation (ITx). High doses of immunosuppres¬sants are needed to prevent rejection but have a negative impact in the long term. Regulatory T cells (T regs) play an important role in the induction of graft tolerance. Our aim is to evaluate the frequency of T regs in the graft and blood with the kinetics of rejection in an experimental intestinal transplant rejection model using tacrolimus, one of the most used immunosuppressive agents in the clinics. Al¬logeneic heterotopic ITxs were performed in rats (Sprague Dawley as donor, Wistar as recipient); tacrolimus 0.6 mg/kg/day was ad-ministrated subcutaneously for 7 days as immunosuppressive ther¬apy. Graft and blood samples were taken at 0, 4, 7, 14, 21 and 28 postoperative days (POD). Wu’ score was used for histopathological diagnosis of acute cellular rejection (ACR). The frequency of T regs (defined as CD4+CD25hiFOXP3+) was determined by flow cytome¬try. Histopathological analysis demonstrated that tacrolimus-treated group developed moderate-severe ACR between 21 and 28 POD (p.0.0001). The frequency of T regs in PBMCs increased during the first 4 POD and then declined to baseline values, while in the graft an increase in T regs was observed at 14 POD and then decreased to baseline levels. Difference in the rejection kinetics and severity were observed in this group compared to previously reported models of allogenic heterotopic ITx without immunosup¬pressant. Although tacrolimus blocks T cell activation and inhibits the production of cytokines such IL-2, our results indicate that T regs generation in the graft and blood is not impaired by immunosuppres¬sive treatment. Rejection progression decrease the relative propor¬tion of Tregs in the graft.