Frequencies of CD4+ 25hi Foxp3+ T cells in long-term follow-up of sirolimus-converted kidney transplant recipients

Background: Tacrolimus(TAC) and Sirolimus(SRL) are commonly used immunosuppressive drugs in kidney transplantation. SRL has been shown to induce the expansion of regulatory T cells in post-transplant recipients converted from TAC to SRL. Methods: This study included 59 renal transplant recipients from a randomized trial of Sirolimus conversion (n=37) or Tacrolimus maintenance (n=22). The conversion started at 12 months post-transplant. Peripheral blood mononuclear cells were collected at baseline, 6, 12, 24, 36 and 48 months postrandomization. T cell subpopulations including intracellular cytokine & transcriptional factor staining were analyzed by flow cytometry. Results: At baseline, the frequencies of CD4+ 25hi Foxp3+ T cells were similar in both groups (0.63±0.06 (SRL) VS 0.66±0.12 (TAC) % of Lymphocytes, p=0.79). SRL conversion led to a significant increase in CD4+ 25hi Foxp3+ T cells at 6, 12 and 24 months post-conversion with highest frequencies observed at 12 months (2.23±0.23 (SRL) VS 0.68±0.12 (TAC) % of Lymphocytes, p<0.01). However, we observed a decline of CD4+ 25hi Foxp3+ T cells started at 24 months and the differences were no longer significant compared to the TAC group at 36 and 48 months post-conversion (1.41±0.17 (SRL) VS 1.07±0.18 (TAC) % of Lymphocytes, p=0.24). The MFI of foxp3 in CD4+ 25hi Foxp3+ T cells was comparable in both groups from baseline to 48 months postconversion. Furthermore, We also observed that CD4+CD5hiFoxp3+ T cells in SRL-converted group had more percentage of cells that co-expressed ROR-gt and IL-17 which are Th17 markers at 24 and 48 months post-conversion. Conclusion: Switching from TAC to SRL results in an expansion of CD4+ 25hi Foxp3+ T cells which peaked at 12 months post-conversion. no significant frequency differences were observed in longer-trem follow-up and we observed more percentage of cells that coexpressed Th17 markers in the SRL group. (Figure Presented).