INTESTINAL TRANSPLANT REJECTION IS DRIVEN BY A DISBALANCE BETWEEN REGULATORY AND INFLAMMATORY IMMUNE STATUS IN THE ALLOGRAFT.

ARRIOLA BENÍTEZ, PAULA CONSTANZA; MACHICOTE, ANDRÉS; PEREZ ILLIDGE L; CASTRO, ARACELI; FUXMAN, CLAUDIA; RAMISCH, DIEGO; RUMBO, M.; FAINBOIM, LEONARDO; GABRIEL GONDOLESI; GENTILINI M.V.

Congreso; Reunión conjunta de sociedades de biociencias 2022; 2022

Background: Acute cellular rejection (ACR) is leading cause of graft loss and morbitidy in intestinal transplant (ITx) patients. Reduction of rejection episodes and induction of immune tolerance are critical to reverse the situation. Regulatory T (T regs) cells have been shown to play a pivotal role in the prevention of rejection in other solid organ transplants. Aim: to evaluate the immunological status during the ACR focusing on the study of CD4 and CD8 Tregs. Material and methods: lamina propria cells of ileum biopsies and explants were isolated from ITx [Non-rejection (NR)=16; Rejection (Rx)= 3] and non-transplant patients [NITx=12]. CD4+ CD25+ Foxp3+ and CD8+HLD-DR+ cells were determined by flow cytometry. Total levels of functional markers of Tregs (Foxp3, TGF-β, IL-10), Th22/17 (RORγ, IL-22, IL-17A), and inflammatory response (IL-1, IL-6) in biopsies [NR=6; Rejection (Rx)=4; NITx=8] were measured by qPCR. CD4+, CD8+, Foxp3+ cells were detected by immunohistochemical staining [NR=40; Rx= 16]. Results: Total percentage of Tregs CD4+ CD25+ Foxp3+ were decreased in ITx patients during the ACR (Rx, p=0.039) in comparison with NITx patients. Although, no changes in Foxp3+ cells were observed (p=0,30), the expression of Foxp3+ mRNA was significantly diminished (p=0,04) accompanied by a tendency to the reduction of the ratio IL-10/IL-17 (p=0,06). RORγ/Foxp3 ratio did not show a different expression between groups (p=0,9). As was expected, CD8+ cells were increased during the ACR (p=0,026), but a reduction of regulatory CD8+HLD-DR+ cells frequency was observed. Significant relative expression of IL-1 (p=0,04) and IL-6 (p=0,01) mRNA demonstrated a proinflammatory immune status during the rejection. Conclusion: our preliminary results indicate that ITx rejection is driven by a disbalance between regulatory and inflammatory immune status in the allograft. Therapies directed to expand Tregs population can potentially be used as an approach to prevent ACR.