Phenotypic characterization of T cells in bronchoalveolar lavage fluid (BALF) and peripheral blood of patients with diffuse panbronchiolitis; the importance of cytotoxic T cells

Abstract

We investigated the contribution of T cells in diffuse panbronchiolitis (DPB) by identifying T cell subsets in BALF of 36 patients with DPB, before and after long-term treatment with macrolide antibiotics, and 16 healthy control subjects. The percentages of lymphocytes and CD3⁺γδ⁺ cells in BALF of DPB patients and control subjects were similar, but the absolute number of these cells was higher in DPB patients. Treatment resulted in a significant reduction in the absolute number of these cells. A further two-colour analysis of T cell subsets in BALF showed a significantly higher ratio and number of CD8⁺HLA-DR⁺ cells in DPB patients. Treatment resulted in a significant reduction of activated T cells. Most BALF CD8⁺ cells were CD8⁺CD11b⁻ cytotoxic T cells. The number of these cells in BALF of DPB patients (26.69 ± 5.86 × 10³/ml) was higher than the control (2.02 ± 0.38 × 10³/ml; P< 0.001), and a significant reduction was observed after treatment (7.69 ± 2.59 × 10³/ml; P< 0.01). The number of CD4⁺ cells was also higher in DPB patients than in controls, and most were CD4⁺CD29⁺ memory T cells. However, treatment did not influence the number of these cells. The number of lymphocytes, CD3⁺γδ⁺, CD8⁺CD11b⁻, CD8⁺HLA-DR⁺, and CD4⁺CD29⁺ cells was higher in patients with bacterial infection than in those without bacterial infection, and interestingly, macrolide therapy reduced the number of lymphocytes, CD3⁺γδ⁺, CD8⁺CD11b⁻ and CD8⁺HLA-DR⁺ cells, irrespective of bacterial infection. In peripheral blood, the percentage of CD8⁺HLA-DR⁺ cells was also higher in DPB patients than in healthy subjects, and significantly decreased after treatment. The percentage of CD8⁺CD11b⁻ cells in peripheral blood was similar in DPB patients and normal subjects, and treatment significantly reduced the percentage of these cells. Finally, the expression of the adhesion molecules CD11a/CD18 (α/β-chains of LFA-1) on lung CD3⁺ cells and CD49d (α-chain of VLA) on lung CD4⁺ cells was enhanced compared with that on peripheral blood in DPB patients. Our results suggest that elevation of memory T cells and activation of CD8⁺ cells, mainly cytotoxic T cells, in the airway lumen of DPB patients may contribute to chronic bronchial inflammation, possibly through up-regulation of adhesion molecules. Our findings also indicate that macrolide antibiotics may have a direct or indirect suppressive effect on cytotoxic T cells, and as such, reduce inflammation and improve clinical condition.

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