Expression of tumor necrosis factor-receptor superfamily members by lung T lymphocytes in interstitial lung disease.
Recently, a novel receptor superfamily has been identified whose members interact with a parallel family of ligands showing homology to tumor necrosis factor (TNF). To investigate the role of these receptor structures in the pulmonary environment, we evaluated the expression of some members of the TNF-receptor (CD27, CD30, CD40, CD95/Fas, CD120a, and CD120b) and TNF-ligand (CD40L, CD70/CD27L, CD30L, and mTNFalpha) superfamilies by bronchoalveolar lavage (BAL) T cells recovered from healthy subjects and patients with interstitial lung disease (ILD). Lung T lymphocytes recovered from control subjects showed a slight expression of CD27 but did not bear CD30, CD40, CD120a, or CD120b antigens. CD27 expression was restricted to normal CD4+ cells. Fas antigen (CD95), which is involved in activation-driven T-cell suicide, and the ligand for CD27 (CD70) were weakly expressed by normal BAL T-cell subpopulations. In patients with sarcoidosis, the majority of pulmonary T lymphocytes were CD4+ cells that expressed low levels of CD27 antigen and an upregulation of CD95 and CD70 molecules. When we characterized lymphocytes accumulating in the lung of patients with HIV infection and hypersensitivity pneumonitis, we demonstrated that T cells accounting for the CD8 alveolitis bore TNF-receptor type 2 (CD120b) at high density and were CD70+ while CD40L, CD30L, or mTNF-alpha expression were not found. The discrete surface expression of the TNF-receptors and TNF-ligands on alveolar T-cell subsets suggests that these molecules play a role in the immune regulatory mechanisms that ultimately lead to the alveolitis in the pulmonary microenvironment of interstitial lung disease.
Agostini
C
C
Padua University School of Medicine, Department of Clinical and Experimental Medicine, Padua, Italy.
Zambello
R
R
Sancetta
R
R
Cerutti
A
A
Milani
A
A
Tassinari
C
C
Facco
M
M
Cipriani
A
A
Trentin
L
L
Semenzato
G
G
D000328:Adult; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology; D015703:Antigens, CD; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000276:immunology / Q000378:metabolism*; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D017565:Sarcoidosis, Pulmonary / Q000276:immunology; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000378:metabolism*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor