Abstract 3042: CD4+ CD25+ Regulatory T-cell Levels Are Associated With Cardiac Allograft Vasculopathy
Cardiac allograft vasculopathy (CAV) is the most important limitation of long-term, post transplant allograft function. Chronic, subclinical inflammation is considered a main trigger of this pathology. Evidence exists, that a regulatory subpopulation of T cells (Tregs) expressing CD4 and CD25 contributes to immune suppression and that inadequate Treg function is associated with clinical acute cellular graft rejection in heart transplant recipients. Whether Tregs play a role in CAV pathogenesis is unknown. A total of 34 patients (mean follow up 111±60 months) were prospectively studied. CAV was determined to be present in 21 patients and absent in 13 by angiography. Heparinized whole blood of patients was stained with fluorescence conjugated monoclonal antibodies directed against CD3, CD4 and CD25 and analyzed by flow cytometry. CD3+ cells were quantified to normalize Treg numbers to total T-cells within the lymphocyte scatter gate. Total CD4+ CD25+ cells were subdivided into CD4+ CD25low and CD4+ CD25high populations. Total CD3+ T-cells were comparable in the CAV (62±13%) and no CAV groups (61±15%). Analysis of total Tregs revealed significant differences between the CAV (15.7±8.9%) and no CAV (8.6±5.1%) groups (p=0.015). Significant changes were also found between CAV and no CAV groups in the CD4+ CD25low (6.16±3.2% vs. 3.92±2.7%; p=0.039) and CD4+ CD25high (9.61±6.22% vs. 4.71±2.66%; p=0.011) populations, respectively. Analysis of the relationship between CD4+ CD25low to CD4+ CD25high showed significantly more CD4+ CD25high (p=0.029) Tregs in the CAV group. Furthermore, total CD4+ CD25+Treg levels correlated with the mean follow-up time after transplantation in all patients examined (rs=0.53; p=0.001). These results show that circulating Treg levels are associated with CAV. A significant shift towards CD4+ CD25high populations also indicates that this subpopulation plays an important role in the pathology of CAV and may indicate an unexpected role for Tregs in chronic allograft rejection. The increased Treg levels identified here may therefore represent a novel, post-transplant immune compensatory mechanism in CAV.