Alterations in CD4+ T-cell Subsets in Living Donor Liver Transplantation Associated With 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 1 year.

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 months 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), and 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 1 month were associated with rejection.