Alterations in CD4+ T-cells subsets after live donor liver transplantation predicts graft rejection

Background and Objectives Regulatory T-cells (Tregs) play a key role in immune homeostasis after organ transplantation. However, the role of CD4+ T cell subsets in early acute rejection is still not well understood. Therefore, our aim was to determine changes in CD4+ T-cell subsets in living donor liver transplantation (LDLT). Methods LDLT patients were assessed for T-cell subsets, Tregs frequencies and their functionality by flow-cytometry at peri and post-transplant in the span of 1year. Results 33 patients were followed-up and 11 (33%) patients have developed early acute cellular rejection (ACR). At peri-transplant time point, MFI of Foxp3+ Tregs was significantly increased compared to HC (P=0.04). However, CD4+CD25+Foxp3+/CD127- Tregs numbers and IL-10, IL-17 and TGF-β secreting functional Tregs were significantly decreased at 3-month compared to peri-transplant (P=0.003). But in patients with rejection, CD4+CD25+FOXP3+ and CD4+CD25+CD127-Tregs were significantly decreased at day 3 compared to no rejection group (P=0.048). Patients with rejection also showed significantly decreased numbers of IL-17 and TGF-β secreting CD4+CD25+FOXP3+ Tregs at peri-transplant time (P=0.04, P=0.03) compared to no rejection. Further, rejection group showed decreased terminally differentiated effector memory (TEMRA) at peri-transplant and day 7 (P=0.048 and P=0.01). Additionally, CD4+ central memory (CM) was decreased at peri-transplant (P=0.05), 1-month (P=0.04), 3 to 6-month (P=0.02). Interpretation and Conclusion Tregs frequencies were significantly decreased in peri-TX in rejection patients. Further, decreased frequencies of CD4+ TEMRA and CD4+ CM at day 7 and 1month were associated with rejection.