Donor-Reactive Regulatory T-Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts.

Background: Acute cellular rejection is a major cause of morbidity after lung transplantation. Because regulatory T (Treg) cells limit rejection of solid organs, we hypothesized that donor-reactive Treg increase after transplantation with development of partial tolerance and decrease relative to conventional CD4+ (Tconv) and CD8+ T cells during acute cellular rejection. Methods: To test these hypotheses, we prospectively collected 177 peripheral blood mononuclear cell specimens from 39 lung transplant recipients at the time of transplantation and during bronchoscopic assessments for acute cellular rejection. We quantified the proportion of Treg, CD4+ Tconv, and CD8+ T cells proliferating in response to donor-derived, stimulated B cells. We used generalized estimating equation-adjusted regression to compare donor-reactive T-cell frequencies with acute cellular rejection pathology. Results: An average of 16.5 +/- 9.0% of pretransplantation peripheral blood mononuclear cell Treg cell were donor-reactive, compared with 3.8% +/- 2.9% of CD4+ Tconv and 3.4 +/- 2.6% of CD8+ T cells. These values were largely unchanged after transplantation. Donor-reactive CD4+ Tconv and CD8+ T-cell frequencies both increased 1.5-fold (95% confidence interval [95% CI], 1.3-1.6; P

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