Effect of maintenance immunosuppressive therapy on FoxP3 and CD28 gene expression in low risk kidney transplant recipients

Background

FoxP3 is a transcription factor expressed by regulatory T cells and is essential for their development and suppressive function. CD28 is a costimulatory receptor on T cells that binds to CD80 and CD86 on antigen-presenting cells, providing a signal required for T cell activation and survival. This study compared FoxP3 and CD28 gene expression in kidney transplant recipients (KTR) maintained on immunosuppressive therapy with mammalian target of rapamycin inhibitors (mTORI) versus calcineurin inhibitors (CNI).

Methods

The expression of FoxP3 and CD28 was assessed in immunologically low-risk KTR with stable graft function. KTR receiving CNI (n = 24) were compared with those who underwent early conversion to mTORI post-transplant (n = 20). All patients received a transplant from living donors and the median time since transplant was 60 months. Gene expression analysis was performed in the peripheral blood mononuclear cells by quantitative PCR.

Results

FoxP3 expression differed significantly between treatment groups, with higher levels observed in the mTORI group compared to the CNI group (P = 0.025), while CD28 expression was comparable between groups. Among KTR receiving CNI therapy, FoxP3 expression was significantly lower in female recipients compared to males (P = 0.008); this difference was not observed in the mTORI group. In a multivariate analysis including age, sex, FoxP3 expression and immunosuppressive therapy, only mTORI therapy was significantly associated with higher estimated glomerular filtration rate [β = 22.66 (95 % CI = 3.41–41.91), P = 0.022].

Conclusions

In stable KTR, long-term immunosuppression with mTORI is associated with higher FoxP3 expression and lower CD28 to FoxP3 expression ratio compared to CNI. Although FoxP3 expression differed between treatment groups, only mTORI therapy was independently associated with improved kidney function.