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Relationship of BAL and Lung Tissue CD4+ and CD8+ T Lymphocytes, and Their Ratio in Idiopathic Pulmonary Fibrosis^*

^* From the Departments of Critical Care and Pulmonary Services (Drs. Papiris, Kapotsis, Roussos, and Daniil, and Mr. Kollintza), Pathology (Dr. Kitsanta), and Hematology (Dr. Karatza), National and Kapodistrian University of Athens, "Evangelismos" Hospital, Athens, Greece; and Meakins-Cristie Laboratories (Dr. Milic-Emili), McGill University, Montreal, QC, Canada.

Correspondence to: Spyros A. Papiris, MD, FCCP, Associate Professor, Department of Critical Care and Pulmonary Services, 45-47 Ipsilantou St, "Evangelismos" Hospital, GR 10675, Athens, Greece; e-mail: papiris{at}otenet.gr

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.

Key Words: BAL • CD4+ • CD8+ • flow cytometry • idiopathic pulmonary fibrosis • immunohistochemistry • inflammation T lymphocytes

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