Conversion From Tacrolimus to Sirolimus Results in Expansion of CD4+25hiFoxp3+ T Cells.

Abstract

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 animal models and human cell cultures but the data in clinical trials are scarce. Methods: This study included 30 renal transplant recipients from a randomized trial of SRL conversion (n=18) or TAC maintenance (n=12). The conversion started at 12 months post-transplant. Peripheral blood mononuclear cells were collected at 0 (baseline), 6, 12 and 24 months post-randomization. T cell subpopulations were analyzed by flow cytometry. Median fluorescent intensity (MFI) of Foxp3 was analyzed by flowjo v10 software. Results: At baseline, the frequencies of CD4+25hiFoxp3+ T cells were similar in both groups (0.25±0.04(SRL) VS 0.39±0.07(TAC) % of PBMC, p=0.10). SRL conversion led to a significant increase in CD4+25hiFoxp3+ T cells at 6, 12 and 24 months post conversion (0.81±0.10(SRL) VS 0.29±0.05(TAC) % of PBMC at 6 months, 0.67±0.10(SRL) VS 0.26±0.06(TAC) % of PBMC at 12 months and 1.58±0.09(SRL) VS 0.13±0.02(TAC) % of PBMC at 24 months (p<0.01 at all time point)).Figure: No Caption available.No frequency difference was observed in other T cell subpopulations. The MFI of foxp3 in CD4+25hiFoxp3+ T cells was comparable in both groups from baseline (105.8±14.3(SRL) VS 112.1±25.8(TAC), p=0.82) to 24 months (75.0±7.1(SRL) VS 98.1±10.8(TAC), p=0.07) post conversion. Conclusion: Switching from TAC to SRL results in a gradual expansion of CD4+25hiFoxp3+ T cells from 6 to 24 months. No significant different in Foxp3 MFI expression was observed between TAC and SRL group suggesting a true increase in regulatory T cells in SRL group. These results might have a clinical impact on immunosuppressive drug selection in kidney transplant patients.