Association of high anti-donor alloreactivity and low frequency of FoxP3-expressing cells prior to kidney transplantation with acute graft rejection

Abstract

Acute rejection (AR) is an important factor for the development of chronic allograft dysfunction following kidney Tx. Identification of patients who would benefit from closer clinical surveillance to allow individual tailoring of immunosuppression and hence reducing the rate of AR is highly desired. Aim of this study was to investigate the association of pre-transplant alloreactivity and frequency of regulatory T cells (T(regs) ) with AR following living-donor kidney Tx. Peripheral blood mononuclear cells were isolated from 40 patients prior to Tx. T-cell alloreactivity against donor and third-party antigen was assessed by proliferative responses in mixed lymphocyte culture and enzyme linked immunospot technique. Pre-transplant frequency of CD4(+) CD25(+) CD127(low) FoxP3(+) T(regs) was determined by flow cytometry. Experimental data were correlated with occurrence of AR. We found that patients with rejection-free (RF) post-Tx courses showed significantly lower pre-transplant alloreactivity to donor antigen compared to individuals with borderline findings (BL) or AR. For RF patients, the proliferative T-cell responses to third-party antigen were significantly higher than for stimulation with donor cells whereas lymphocytes of the AR group showed the inverse pattern. A significantly higher expression of FoxP3 within the CD4(+) CD25(+) CD127(low) subset for RF and BL compared to the AR group was observed. In conclusion, pre-transplant anti-donor alloreactivity and FoxP3 expression within the CD4(+) CD25(+) CD127(low) subpopulation might prove useful to further define the patient's risk for AR.