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Lymphocytic Bronchiolitis Is Associated With Inadequate Suppression of Blood T-Cell Granzyme B, IFN-gamma, and TNF-alpha

  作者 Hodge, G; Hodge, S; Li-Liew, C; Chambers, D; Hopkins, P; Reynolds, PN; Holmes, M  
  选自 期刊  Transplantation;  卷期  2010年89-10;  页码  1283-1289  
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[摘要]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 013, 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 regimensMethods. 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

 
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