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T lymphocytes are crucial in lung allorejection. The contribution of lymphocyte subtypes to the pathogenesis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) remains unclear.Twenty-nine initially healthy lung transplant recipients underwent 136 bronchoscopic assessments, including bronchoalveolar lavage (BAL) (with flow cytometry) and endobronchial biopsies (EBB) (with immunohistochemistry) over 3 years of follow-up.Of the 29 patients studied over 3 years, 23 developed BOS category 0p and 17 went on to BOS 1. Compared with controls, the BAL percentage of CD4+ cells was lower and the percentage of CD8+ cells was increased significantly early posttransplant. Subsequent BAL lymphocyte subtype changes with time, or with the development of BOS, were minimal. By contrast, the early posttransplant EBB lymphocyte numbers were normal (P>0.05 vs. controls); subsequently, CD3+ and CD8+ (but not CD4+) cells were increased with time in patients who did not develop BOS (P<0.05) and, more strikingly, in patients who eventually developed BOS (P<0.01). Multivariate analyses suggested an association between BAL lymphocytes (percentage) and azathioprine dose, female gender, rejection grade A on transbronchial biopsies, and pre-BOS status, whereas EBB CD8+ cell counts were associated with time posttransplant, pretransplant diagnosis, and rejection grade B on TBB.There is an early, persistent low percentage of BAL CD4+ T cells, high BAL CD8+ T cells, and progressively increasing airway wall CD3+ and CD8+ T cells with time posttransplant in healthy patients (but more predominantly in BOS patients) after transplantation. These immunopathologic changes may suggest that CD8+ T cells could escape current immunosuppression and participate in chronic lung rejection.