Original articleGeneral thoracicRespiratory Virus-Induced Dysregulation of T-Regulatory Cells Leads to Chronic Rejection
Section snippets
Human Subjects
Blood specimens were collected from patients undergoing lung transplantation and normal volunteers at the Barnes-Jewish Hospital after obtaining informed consent in accordance with a protocol approved by the Institutional Review Board. Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood by Ficoll-Hypaque density gradient centrifugation, and stored at −135°C. Plasma was stored at −70°C. Bronchiolitis obliterans syndrome was defined according to the standard
Loss of Treg During Respiratory Viral Infections in Human Lung Transplant Recipients
The clinical and demographic profile of study subjects (n = 30) is shown in Table 1. We determined the frequency of Treg in lung transplant recipients at 2 to 4 month intervals using PBMC. The median onset of BOS was 45 months. As shown in Table 2, 13 of the thirty patients (43.3%) revealed a trough as defined by a drop in the frequency of Treg greater than 50% of the baseline, prior to the development of BOS. Of the patients who revealed Treg trough (n = 13), 9 (69.2%) had a single trough, 3
Comment
Bronchiolitis obliterans syndrome remains the major cause of poor long-term lung allograft survival [11, 16]. The development of BOS is highly complex and involves multiple pathways. It is generally believed that both alloimmune dependent and independent pathways contribute to BOS [1]. There is increasing evidence that alterations in pathways responsible for maintenance of peripheral tolerance may play a crucial role in chronic rejection. In support of this, studies have shown that Treg play an
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