Exploring Immunological Features of an Experimental Model of Heterotopic Allogeneic Intestinal Transplantation in Rodents: From Blood to Graft

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

San Luis

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología; 2023

Sociedad Argentina de Inmunología

Graft rejection is one of the most common complications associated withintestinal transplantation (ITx) and correlates with graft injury, leading to microbialtranslocation and subsequent sepsis. High doses of immunosuppressants areneeded in order to prevent the allogeneic response, but have a negative impactin the long term. Goblet cells (GC) actively secrete mucus to the intestinal lumen,serving a vital role in mucosal protection, therefore, their depletion potentiallyincreases microbial translocation risk. Regulatory T cells (T regs) are majorplayers in the induction of graft tolerance. On the other hand, donor-specificantibodies (DSAs) have a key role on antibody-mediated rejection.Our aim was to characterize an experimental ITx model in rodents employingtacrolimus, a widely used immunosuppressive agent in clinical settings,evaluating the frequency of T regs in the graft, and establishing its correlation withthe rejection kinetics, GC quantity, and DSAs presence in recipients' sera.Allogeneic heterotopic ITxs were performed in rats (Sprague Dawley strain asdonor, Wistar as recipient; n=6); tacrolimus 0.6 mg/kg/day was administeredsubcutaneously for 7 days as immune suppressive therapy. Graft samples weretaken at 0, 7, 14, 21 and 28 postoperative days (POD). Wu’ score was used forhistopathological diagnosis of acute cellular rejection (ACR). Flow cytometryassays were used to determine frequency of Tregs in graft (defined asCD4+CD25highFOXP3+) and DSAs levels in serum. Alcian Blue staining was usedto count GC in graft samples.Histopathological analysis demonstrated that tacrolimus-treated group developedmoderate-severe ACR between 21 and 28 POD (p