Compartmentalized activation of the interleukin 2 gene by lung T lymphocytes in active pulmonary sarcoidosis.
Gene Expression Regulation
Sarcoidosis is a systemic disorder characterized by the accumulation of large numbers of interleukin 2 (IL 2) releasing helper (Leu-3+) T cells in involved organs. To determine whether the IL 2 gene is activated in sarcoidosis T cells in a systemic manner or only at sites of disease, cells obtained by bronchoalveolar lavage of individuals with active sarcoidosis, inactive sarcoidosis, and normals were evaluated for the spontaneous presence of IL 2 transcripts by using a human IL 2 cDNA probe and Northern analysis of extracted RNA. Freshly recovered lung cells of individuals with active pulmonary sarcoidosis contained 0.85 kilobase pairs (kb) IL 2 mRNA transcripts. In contrast, no IL 2 mRNA transcripts could be detected in fresh autologous blood T cells or in purified autologous blood Leu-3+ T cells, although IL 2 mRNA transcripts were inducible in these cells by phytohemaglutinin/phorbol myristic acetate. The sarcoid lung T cells, however, did not express the IL 2 gene constitutively; when placed in culture with no stimulation and evaluated after 24 hr, they demonstrated down regulation of the amounts of IL 2 mRNA transcripts, despite the fact that they were capable of re-expressing the IL 2 gene and releasing more IL 2 in response to added activation signals. Thus the activation of the IL 2 gene in T cells in active sarcoidosis occurs at the sites of disease and is not a generalized property of T cells throughout the body, and is not sustained if the T cells are removed from the sites of disease. Although the cause of sarcoid is unknown, these observations are consistent with the concept that sarcoid is associated with local stimuli at the site of disease eliciting the Leu-3+ T cell IL 2 gene activation that plays such a critical role in the pathogenesis of this disease.