MODELING INTESTINAL TRANSPLANT REJECTION: A COMPARATIVE EXPERIMENTAL AND CLINICAL STUDY

Background: Graft rejection remains a major challenge in intestinal transplantation (IT).Tacrolimus improves graft survival but has adverse effects with long-term use.We characterized an experimental IT rejection model under short-term and long-term tacrolimus treatment, analyzing rejection kinetics, immune dynamics, and gene expressions and compared with clinical rejection samples.Methods: Allogeneic IT was performed in rats.Recipients were divided into a non-immunosuppressed group (n-IS), a short-term tacrolimus group (st-TAC), and a long-term tacrolimus group (lt-TAC).Graft samples were collected weekly.Treg frequencies were assessed by flow-cytometry, proinflammatory (CXCL10, IFNg, CXCL11, IDO) and Th2/eosinophilic markers (IL-13, CCR3) by qPCR, and eosinophilic infiltration by Congo-Red staining were analyzed.Human IT rejection biopsies were classified by rejection severity, infiltrate type and CXCL10/IFNg expression levels.Results: Tacrolimus improved post-transplant survival (p<0.0001).In contrast to the lt-TAC group, n-IS and st-TAC groups developed severe rejection (10 and 21POD, respectively), although st-TAC grafts exhibited variable rejection kinetics.Severe rejection correlated with increased CXCL10, CXCL11, IFNg, and IDO expression.IL-13 and CCR3 upregulation, along with eosinophilic infiltration, were observed exclusively in st-TAC grafts at 21POD.Early Treg expansion occurred in all groups(p<0.05),followed by a return to baseline, except in a subset of st-TAC grafts, which remained elevated Treg levels.In clinical samples from rejection episodes of lymphoplasmacytic rejection infiltrate correlated with higher CXCL10 and IFNg expression compared to mixed or hypocellular infiltrate(p<0.05).Conclusions: The heterogeneity in rejection severity and immune markers observed in the experimental st-TAC group resembled clinical rejection phenotypes, suggesting that immunosuppression levels may influence rejection response pathways involved.