CD27 expression on CD4+ T cells differentiates effector from regulatory T cell subsets in the lung

Area of Science:

• Immunology
• Pulmonary Medicine
• Occupational Health

Background:

• Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium exposure.
• CBD is characterized by CD4(+) T cell alveolitis and lung fibrosis.
• Beryllium-specific CD4(+) T cells in the lung exhibit an effector memory phenotype and recognize beryllium antigen independently of CD28.

Purpose of the Study:

• To investigate the expression of the costimulatory molecule CD27 on beryllium-responsive CD4(+) T cells in the lungs of CBD patients.
• To determine the relationship between CD27 expression on lung T cells and markers of inflammation.
• To identify and characterize regulatory T cells (Tregs) within the CD4(+) T cell population in the lungs.

Main Methods:

• Flow cytometry analysis of CD4(+) T cells from bronchoalveolar lavage (BAL) and peripheral blood of CBD patients.
• Assessment of CD27 and CD25 expression on T cells.
• Evaluation of FoxP3 expression to identify regulatory T cells (Tregs).
• Functional assessment of suppressor activity of identified Treg populations.

Main Results:

• The majority of beryllium-responsive CD4(+) T cells in BAL from CBD patients have lost CD27 expression.
• Loss of CD27 expression on BAL CD4(+) T cells inversely correlates with lung inflammation markers.
• A subset of CD4(+)CD27(+) T cells in BAL contains FoxP3-expressing Tregs, which coexpress CD25.
• CD27 and CD25 coexpression effectively identifies potent suppressor functional Tregs in both blood and BAL.

Conclusions:

• CD27 expression is differentially regulated on effector T cells within the inflamed lung microenvironment in CBD.
• CD27 loss on lung-infiltrating CD4(+) T cells is associated with disease activity.
• The CD27/CD25 coexpression profile can be utilized to isolate and functionally assess Tregs in the context of chronic beryllium disease.