Expression of thioredoxin in granulomas of sarcoidosis: possible role in the development of T lymphocyte activation

Background-Activated T lymphocytes are one of the characteristic features o f sarcoidosis. The mechanism of T cell activation, expressing various activ ation markers including interleukin 2 receptor (IL-2R), has been extensivel y investigated but the precise mechanism remains unknown. Although thioredo xin (TRX) displays a number of biological activities including IL-2R induci ng activity, its role in the induction of IL-2R expression on T cells in sa rcoidosis has not been determined. The expression of TRX and IL-2R in granu lomas of patients with sarcoidosis has been studied to clarify a possible r ole for TRX in the induction of IL-2R expression. Methods-Granulomas in specimens of lung tissue and lymph nodes from five pa tients with sarcoidosis were immunohistochemically stained with anti-TRX an tibody and anti-IL-2R alpha chain antibody and the concentration of TRX in the bronchoalveolar lavage (BAL) fluid from 20 patients with pulmonary sarc oidosis was measured. Results-Granulomas in lung and lymph node tissue from patients with sarcoid osis showed strong reactivity with anti-TRX antibody. Positive staining was present in the macrophages, epithelioid cells, and Langhans' type giant ce lls but not in lymphocytes. IL-2R was expressed on lymphocytes in the same granulomas. By contrast, positive immunoreactivity was not found in lung ti ssue specimens from 12 control subjects. Concentrations of TRX in BAL fluid were higher in patients with pulmonary sarcoidosis (median (range) 122.6 ( 20.9-303.3) ng/ml) than in control subjects (32.9 (16.8-52.8) ng/ml, p<0.05 ). Conclusions-TRX is highly expressed and is locally produced by granulomas i n patients with sarcoidosis. The coexistence of immunoreactive TRX and IL-2 R in the same granulomas suggests that TRY might act as a local inducing fa ctor for IL-2R expression on T cells.