Koura T, Gon Y, Hashimoto S, Azuma A, Kudoh S, Fukuda Y, Sugawara I, Yodoi J, Horie T
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Thorax. 2000 Sep;55(9):755-61. doi: 10.1136/thorax.55.9.755.
Activated T lymphocytes are one of the characteristic features of sarcoidosis. The mechanism of T cell activation, expressing various activation markers including interleukin 2 receptor (IL-2R), has been extensively investigated but the precise mechanism remains unknown. Although thioredoxin (TRX) displays a number of biological activities including IL-2R inducing activity, its role in the induction of IL-2R expression on T cells in sarcoidosis has not been determined. The expression of TRX and IL-2R in granulomas of patients with sarcoidosis has been studied to clarify a possible role for TRX in the induction of IL-2R expression.
Granulomas in specimens of lung tissue and lymph nodes from five patients with sarcoidosis were immunohistochemically stained with anti-TRX antibody and anti-IL-2Ralpha chain antibody and the concentration of TRX in the bronchoalveolar lavage (BAL) fluid from 20 patients with pulmonary sarcoidosis was measured.
Granulomas in lung and lymph node tissue from patients with sarcoidosis showed strong reactivity with anti-TRX antibody. Positive staining was present in the macrophages, epithelioid cells, and Langhans' type giant cells but not in lymphocytes. IL-2R was expressed on lymphocytes in the same granulomas. By contrast, positive immunoreactivity was not found in lung tissue 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).
TRX is highly expressed and is locally produced by granulomas in patients with sarcoidosis. The coexistence of immunoreactive TRX and IL-2R in the same granulomas suggests that TRX might act as a local inducing factor for IL-2R expression on T cells.
活化的T淋巴细胞是结节病的特征之一。T细胞活化机制，包括表达各种活化标志物如白细胞介素2受体（IL-2R），已得到广泛研究，但确切机制仍不清楚。尽管硫氧还蛋白（TRX）具有多种生物学活性，包括诱导IL-2R的活性，但其在结节病T细胞上诱导IL-2R表达中的作用尚未确定。研究结节病患者肉芽肿中TRX和IL-2R的表达，以阐明TRX在诱导IL-2R表达中的可能作用。
对5例结节病患者的肺组织和淋巴结标本中的肉芽肿，用抗TRX抗体和抗IL-2Rα链抗体进行免疫组织化学染色，并测定20例肺结节病患者支气管肺泡灌洗（BAL）液中TRX的浓度。
结节病患者肺和淋巴结组织中的肉芽肿对抗TRX抗体显示出强反应性。巨噬细胞、上皮样细胞和朗汉斯型巨细胞呈阳性染色，而淋巴细胞中未出现。同一肉芽肿中的淋巴细胞表达IL-2R。相比之下，12例对照受试者的肺组织标本中未发现阳性免疫反应性。肺结节病患者BAL液中TRX的浓度（中位数（范围）122.6（20.9 - 303.3）ng/ml）高于对照受试者（32.9（16.8 - 52.8）ng/ml，p<0.05）。
TRX在结节病患者中高表达且由肉芽肿局部产生。同一肉芽肿中免疫反应性TRX和IL-2R的共存表明，TRX可能作为T细胞上IL-2R表达的局部诱导因子。
