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 membe rs interact with a parallel family of ligands showing homology to tumo r necrosis factor (TNF). To investigate the role of these receptor str uctures in the pulmonary environment, we evaluated the expression of s ome members of the TNF-receptor (CD27, CD30, CD40, CD95/Fas, CD120a, a nd CD120b) and TNF-ligand (CD40L, CD70/CD27L, CD30L, and mTNF alpha) s uperfamilies by bronchoalveolar lavage (BAL) T cells recovered from he althy subjects and patients with interstitial lung disease (ILD). Lung T lymphocytes recovered from control subjects showed a slight express ion of CD27 but did not bear CD30, CD40, CD120a, or CD120b antigens. C D27 expression was restricted to normal CD4(+) cells. Fas antigen (CD9 5), which is involved in activation-driven T-cell suicide, and the lig and for CD27 (CD70) were weakly expressed by normal BAL T-cell subpopu lations. In patients with sarcoidosis, the majority of pulmonary T lym phocytes were CD4(+) cells that expressed low levels of CD27 antigen a nd an upregulation of CD95 and CD70 molecules. When we characterized l ymphocytes accumulating in the lung of patients with HIV infection and hypersensitivity pneumonitis, we demonstrated that T cells accounting for the CD8 alveolitis bore TN F-receptor type 2 (CD120b) at high den sity and were CD70(+) while CD40L, CD30L, or mTNF-alpha expression wer e not found. The discrete surface expression of the TNF-receptors and TNF-ligands on alveolar T-cell subsets suggests that these molecules p lay a role in the immune regulatory mechanisms that ultimately lead to the alveolitis in the pulmonary microenvironment of interstitial lung disease.