Association of CD4+CD25highFoxP3+ regulatory T-cell frequency with graft outcome upon Fk506 treatment in an experimental small bowel transplantation model

RODRIGO PAPA-GOBBI; PABLO STRINGA; MARIANA MACHUCA; ANE ANDRÉS; IVANA IVANOFF MARINOFF; NIDIA ARREOLA; JAVIER SERRADILLA; MARTÍN RUMBO; FRANCISCO HERNÁNDEZ-OLIVEROS

Buenos Aires

Congreso; 29th International Congress of The Transplantation Society (TTS 2022); 2022

The Transplantation Society (TTS)

Background: Intestinal transplantation (ITx) is the only curative option in patients withirreversible intestinal failure showing complications in parenteral nutrition. However, theimmunological load of the gut makes the rejection rate to be higher than the rest of solidorgan transplants (80% within the ¦rst 90 days after surgery), the graft loss rate and need forre-transplantation at 1, 5, and 10 years 29%, 50%, and 59%, respectively, and the 10-yearsurvival of only 43%. Therefore, new strategies aiming to down modulate host vs. graftresponse are crucial to improve ITx long term results. Regulatory T-cells (Tregs) are keyplayers in the induction/maintenance of peripheral tolerance, nonetheless their relevance inITx in almost unexplored. We study the Treg migration/expansion kinetic and its associationwith the allograft outcome in an experimental ITx model.Methods: We used a rat heterotopic and allogenic ITx model in which Brown Norway smallbowel (jejunum and ileum) was engrafted into Lewis animals. Recipients were randomlydivided into 4 groups (n=5): no immunosuppressant treatment, Rapamycin (2 mg/kg), Fk506(0.6 mg/kg) treatment for 14 days, and Fk506 (0.6 mg/kg) treatment for 7 days and 7 dayswithout immunosuppression. Blood and intestinal biopsies were taken before graftreperfusion and 3, 7, and 14 days after surgery. Acute cellular rejection (ACR) was diagnosedby clinical/histological ¦ndings, gene expression of pro- and anti-in§ammatory mediatorsquanti¦ed by RT-qPCR and T-cell chimerism/Tregs frequency analyzed by §ow cytometry.Results: Rapamycin and non-treated animals showed signi¦cant clinical and histologicaldeterioration since day 7 post-transplant (mild-moderate ACR at day 7 and severe ACR at thedays 10-12, p