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; MACHUCA MARIANA; 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 inpatients with irreversible intestinal failure showing complications in parenteralnutrition. However, the immunological load of the gut makes the rejection rateto be higher than the rest of solid organ transplants (80% within the first 90days after surgery), the graft loss rate and need for re-transplantation at 1,5, and 10 years 29%, 50%, and 59%, respectively, and the 10-year survivalof only 43%. Therefore, new strategies aiming to down modulate host vs.graft response are crucial to improve ITx long term results. Regulatory T-cells(Tregs) are key players in the induction/maintenance of peripheral tolerance,nonetheless their relevance in ITx in almost unexplored. We study the Tregmigration/expansion kinetic and its association with the allograft outcome inan experimental ITx model.Methods: We used a rat heterotopic and allogenic ITx model in which BrownNorway small bowel (jejunum and ileum) was engrafted into Lewis animals.Recipients were randomly divided into 4 groups (n=5): no immunosuppressant treatment, Rapamycin (2mg/kg), Fk506 (0.6mg/kg) treatment for 14days, and Fk506 (0.6mg/kg) treatment for 7 days and 7 days without immunosuppression. Blood and intestinal biopsies were taken before graft reperfusion and 3, 7, and 14 days after surgery. Acute cellular rejection (ACR)was diagnosed by clinical/histological findings, gene expression of pro- andanti-inflammatory mediators quantified by RT-qPCR and T-cell chimerism/Tregs frequency analyzed by flow cytometry.Results: Rapamycin and non-treated animals showed significant clinical andhistological deterioration since day 7 post-transplant (mild-moderate ACR atday 7 and severe ACR at the days 10-12, p