Lymphocytic bronchiolitis is associated with inadequate suppression of blood T-cell granzyme B, IFN-γ, and TNF-α

Abstract

Background. Lymphocytic bronchiolitis (LB) has been shown to be an important factor for the subsequent development of obliterative bronchiolitis (OB). We have previously shown that OB, which limits long-term survival after lung transplantation, is associated with lack of suppression of peripheral blood T-cell granzyme B, interferon (IFN)-[gamma], and tumor necrosis factor (TNF)-[alpha]. However, the role of these proinflammatory mediators in LB is unknown. We hypothesized that these proinflammatory mediators may also be increased during LB episodes despite standard immunosuppression regimens. Methods. T-cell intracellular cytokine profiles and granzyme B were studied in whole blood, bronchoalveolar lavage samples, and bronchial brushings from stable lung transplant patients with LB and from healthy controls, using multiparameter flow cytometry. Results. There was a significant increase in peripheral blood T-cell granzyme B and CD8+ T-cell IFN-[gamma] and TNF-[alpha] in patients with LB compared with control and stable groups and a decrease in CD25+CD127-CD3+CD8- T regulatory cells in stable and LB transplant patients compared with controls. No changes were noted in the airways. Conclusions. LB is associated with inadequate suppression of peripheral blood T-cell granzyme B, IFN-[gamma], and TNF-[alpha]. Drugs that effectively reduce these proinflammatory mediators may improve current protocols for treating LB and possibly reduce subsequent progression to OB in lung transplant patients.