FOXP3-Positive Regulatory Cells Inside the Allograft and the Correlation With Rejection

Abstract

Background Foxp3 is a transcription factor associated with regulatory T cells. Little is known about the role of Foxp3+ regulatory T cells in relation to graft rejection in humans. Methods By using a quantitative polymerase chain reaction assay, we measured the levels of messenger RNA (mRNA) for Foxp3 in 27 samples obtained at allograft nephrectomy for acute nonvascular rejection (ANVR; n = 7), or acute vascular rejection (AVR; n = 15), or loss due to a nonimmune cause (LNIC; n = 5, as control). Granzyme B was also analyzed as a positive control for the host-driven immune response. Results Median Foxp3 mRNA levels correlated with the severity of rejection: LNIC 1.000, ANVR 1.429, and AVR 3.904 ( P = .022 for LNIC and AVR by the Kruskal-Wallis test). The receiver operating characteristic curve for AVR demonstrated an area under the curve of 0.733 ( P = .04; 95% CI, 0.528–0.939). The levels of granzyme B mRNA also showed the same profile but did not reach statistical significance. Conclusions The presence of mRNA for Foxp3 inside the graft suggested specific homing during severe episodes of acute rejection. Its presence may indicate the development of host immunoregulatory responses during the ongoing cytolytic activity. In addition, assessment of Foxp3 mRNA inside the graft may distinguish vascular from nonvascular rejection.