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 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+ gammadelta+ 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 x 10(3)/ml) was higher than the control (2.02 +/- 0.38 x 10(3)/ml; P < 0.001), and a significant reduction was observed after treatment (7.69 +/- 2.59 x 10(3)/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+ gammadelta+, 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+ gammadelta+, 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 (alpha/beta-chains of LFA-1) on lung CD3+ cells and CD49d (alpha-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.
Kawakami
K
K
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Kadota
J
J
Iida
K
K
Fujii
T
T
Shirai
R
R
Matsubara
Y
Y
Kohno
S
S
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000503:physiopathology; D001773:Blood Cells / Q000166:cytology; D001988:Bronchiolitis / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D000900:Anti-Bacterial Agents; D015815:Cell Adhesion Molecules; D018942:Macrolides