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"Kapotsis, George"
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CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis
2005
BackgroundSeveral studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea.MethodsSurgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+TLs, CD4+TLs, and CD8+TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale.ResultsElastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD68+ cells for the 16.6% ± 2, CD3+ TLs for the 28.8% ± 7, CD4+ TLs for the 14.5 ± 4 and CD8+ TLs for the 13.8 ± 4. CD8+TLs correlated inversely with FVC % predicted (rs = -0.67, p = 0.01), TLC % predicted (rs = -0.68, p = 0.01), DLCO % predicted (rs = -0.61, p = 0.04), and PaO2 (rs = -0.60, p = 0.04). Positive correlations were found between CD8+TLs and P(A-a)O2 (rs = 0.65, p = 0.02) and CD8+TLs and MRC score (rs = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (rs = -0.80, p = 0.002) and FEV1 % predicted (rs = -0.68, p = 0.01).ConclusionIn UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.
Journal Article
Relationship of BAL and Lung Tissue CD4+ and CD8+ T Lymphocytes, and Their Ratio in Idiopathic Pulmonary Fibrosis
2005
Background: Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary
fibrosis (IPF) and might play a pathogenetic role. BAL, a far less invasive technique, has also been used for the investigation
of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition
of the lung parenchyma.
Study objective: To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid.
Patients and methods: Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens of 12 untreated
patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis
(SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry.
Results: In lung tissue, CD3+ TLs accounted for a mean (± SEM) of 28.8 ± 7% of total cells, CD4+ TLs accounted for 14.5 ± 4% of total
cells (50.1 ± 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 ± 4% of total cells (47.4 ± 4% of CD3+ TLs). In BAL fluid,
lymphocytes accounted for 9.8 ± 2.5% of total cells, CD4+ TLs accounted for 51.8 ± 4% of CD3+ TLs, and CD8+ TLs accounted
for 42.2 ± 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with
the number of CD4+ and CD8+ TLs in BAL fluid ( r = 0.846 and p = 0.001 vs r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio
found in tissue and BAL fluid (1.05 ± 0.21 and 1.5 ± 0.27, respectively; r = 0.832; p = 0.01).
Conclusion: The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration
in pulmonary parenchyma.
Journal Article
Relationship of BAL and Lung Tissue CD4+ and CD8+ T Lymphocytes, and Their Ratio in Idiopathic Pulmonary Fibrosis
by
Milic-Emili, Josef
,
Papiris, Spyros A.
,
Kollintza, Androniki
in
Biological and medical sciences
,
Biopsy
,
Bronchoalveolar Lavage Fluid - cytology
2005
Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary fibrosis (IPF) and might play a pathogenetic role. BAL, a far less invasive technique, has also been used for the investigation of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition of the lung parenchyma.
To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid.
Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens of 12 untreated patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry.
In lung tissue, CD3+ TLs accounted for a mean (± SEM) of 28.8 ± 7% of total cells, CD4+ TLs accounted for 14.5 ± 4% of total cells (50.1 ± 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 ± 4% of total cells (47.4 ± 4% of CD3+ TLs). In BAL fluid, lymphocytes accounted for 9.8 ± 2.5% of total cells, CD4+ TLs accounted for 51.8 ± 4% of CD3+ TLs, and CD8+ TLs accounted for 42.2 ± 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with the number of CD4+ and CD8+ TLs in BAL fluid (r = 0.846 and p = 0.001 vs r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio found in tissue and BAL fluid (1.05 ± 0.21 and 1.5 ± 0.27, respectively; r = 0.832; p = 0.01).
The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration in pulmonary parenchyma.
Journal Article