The frequency of peripheral PD-1+ TCD4+ cells is reversely associated with serum creatinine levels in recipients of kidney allografts

The long-term survival of solid organ allografts remains a challenge for organ transplantation systems worldwide. T-cell exhaustion has been supposed to be associated with immunologic tolerance in transplantation and might reflect the immunologic status in recipients. The aim of the present study was to compare the TCD4+ cells of kidney transplant recipients with high and low serum creatinine levels for their expressions of PD-1 and TIGIT as two well-known exhaustion markers. Blood samples were taken from 20 kidney allograft recipients with serum creatinine levels above 2 mg/dL and 20 recipients with creatinine levels below 2 mg/dL. The percentages of PD-1+ CD4+ and TIGIT+ CD4+ cells were analyzed along with the evaluation of TNF-α, IFN-γ, and IL-10 release from peripheral blood mononuclear cells (PBMCs). The patients with serum creatinine levels below 2 mg/dL demonstrated a higher frequency of PD-1+ CD4+ T-cells (p = 0.003) along with lower TNF-α secretion from PBMCs (p = 0.028). The frequency of PD-1 + CD4+ T-cells was reversely correlated with the serum creatinine levels in recipients of kidney allografts (r = 0.59, p < 0.001). Besides, the MFI of TIGIT on TCD4+ cells demonstrated a trend for higher expression in patients with serum creatinine levels below 2 mg/dL (p = 0.070). The expression of PD-1+ on CD4+ T-cells demonstrated a potential for estimation of the immunologic status of the host in interaction with alloantigens. The exhaustion markers could be regarded as potential diagnostic indicators for the evaluation of immunologic tolerance in renal transplantation.