The aim of this study was to determine whether the abundance of regulatory T cells (Tregs) ( C D 4 + C D 2 5 h i g h ) affects the de novo development of anti-HLA donor-specific antibodies (DSAs) in kidney transplant recipients (KTRs). Methods. Unsensitized (PRA ≤ 10%, no DSA) adult primary KTRs who received a living (83%) or deceased (17%) KT in our Institution during 2004/2005 were included. DSA testing was performed monthly, and Tregs were quantified by flow cytometry every 3 months, during the 1st year after KT. All patients received triple drug immunosuppressive therapy (CNI + MMF or AZA + PDN); 83% received anti-CD25. Results. 53 KTRs were included; 32% developed DSA during the 1st year after KT. Significantly lower 7-year graft survival was observed in those who developed DSA. No difference was observed in Treg numbers up to 9 months after KT, between DSA positive and negative. However, at 12 months after KT, DSA-negative patients had significantly higher numbers of Treg. Conclusions. Early development of DSA was not associated to variations in Treg abundance. The differences in Treg numbers observed at the late time point may reflect better immune acceptance of the graft and may be associated to long-term effects. Additional inhibitory mechanisms participating earlier in DSA development after KT deserve to be sought. 1. Introduction Effective immunosuppressive regimens have greatly improved the early survival of renal allografts. However, the rate of late allograft loss has remained relatively constant [1]. This is probably related to the fact that late allograft dysfunction not only results from immune-mediated damage, but also occurs as the consequence of a complex series of events that include arterial fibrointimal thickening, interstitial fibrosis, and tubular atrophy [2–4]. The presence of donor-specific antibodies (DSAs) directed against human leukocyte antigens (HLAs) has been associated in a growing number of reports to poor prognosis of renal allografts [5–7]. The association between anti-HLA antibodies and poor renal allograft evolution is explained by diverse alloantibody-mediated clinical syndromes, ranging from hyperacute rejection [8], early and late acute alloantibody-mediated rejection [9–11], and chronic humoral rejection [12]. In contrast to the well-known acute and devastating effects of preformed antibodies, de novo produced antibodies against an implanted graft do not cause immediate failure [7]. However, de novo antibodies may eventually cause chronic graft rejection [13, 14]. The presence of DSA implies that B-cells
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