PHENOTYPIC CHARACTERIZATION OF T-CELLS IN BRONCHOALVEOLAR LAVAGE FLUID (BALF) AND PERIPHERAL-BLOOD OF PATIENTS WITH DIFFUSE PANBRONCHIOLITIS - THE IMPORTANCE OF CYTOTOXIC T-CELLS

We investigated the contribution of T cells in diffuse panbronchioliti s (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(+) gamma delta(+) cells in BALF of DPB patients and control subjects wer e similar, but the absolute number of these cells was higher in DPB pa tients. 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 reduc tion 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+/-5.86x10(3)/ml) was higher than the control (2.02+/-0.38x10(3)/ ml; P<0.001), and a significant reduction was observed after treatment (7.69+/-2.59x10(3)/ml, P<0.01). The number of CD4(+) cells was also h igher in DPB patients than in controls, and most were CD4(+)CD29(+) me mory T cells. However, treatment did not influence the number of these cells. The number of lymphocytes, CD3(+) gamma delta(+), CD8(+)CD11b( -), CD8(+) HLA-DR(+), and CD4(+)CD29(+) cells was higher in patients w ith bacterial infection than in those without bacterial infection, and interestingly, macrolide therapy reduced the number of lymphocytes, C D3(+) gamma delta(+), CD8(+)CD11b(-) and CD8(+) HLA-DR(+) cells, irres pective of bacterial infection. In peripheral blood. the percentage of CD8(+) HLA-DR(+) cells was also higher in DPB patients than in health y subjects, and significantly decreased after treatment. The percentag e of CD8(+)CD11b(-) cells in peripheral blood was similar in DPB patie nts and normal subjects, and treatment significantly reduced the perce ntage of these cells. Finally, the expression of the adhesion molecule s CD11a/CD18 (alpha/beta-chains of LFA-1) on lung CD3(+) cells and CD4 9d (alpha-chain of VLA) on lung CD4(+) cells was enhanced compared wit h that on peripheral blood in DPB patients. Our results suggest that e levation of memory T cells and activation of CD8(+) cells. mainly cyto toxic T cells, in the airway lumen of DPB patients mau contribute to c hronic bronchial inflammation, possibly through up-regulation of adhes ion molecules. Our findings also indicate that macrolide antibiotics m ay have a direct or indirect suppressive effect on cytotoxic T cells, and as such, reduce inflammation and improve clinical condition.