Thymomas alter the T-cell subset composition in the blood:: a potential mechanism for thymoma-associated autoimmune disease
Thymomas alter the T-cell subset composition in the blood:: a potential mechanism for thymoma-associated autoimmune disease
复制标题
DOI：
10.1182/blood.v96.12.3872.h8003872_3872_3879
复制
发表时间：
2000-12-01
期刊：
影响因子：
20.3
通讯作者：
Marx, A
中科院分区：
文献类型：
--
作者：
Hoffacker, V;Schultz, A;Marx, A
胸腺瘤是唯一被证明可以从不成熟的前体细胞产生成熟 T 细胞的肿瘤。然而，尚不清楚瘤内胸腺生成是否对外周 T 细胞池有影响，因此可能与胸腺瘤相关重症肌无力的高频率有关。这项研究表明，使用基于荧光激活细胞分选的分析和 T 细胞增殖测定，胸腺瘤中的胸腺生成和 T 细胞功能与血液中的免疫学改变相对应。具体而言，与正常对照相比，胸腺瘤患者中循环CD45RA(+)CD8(+) T细胞的比例显着增加，这与异常偏向CD8(+)表型的瘤内T细胞发育一致。而且，胸腺切除术后循环CD45RA(+)CD8(+) T细胞的比例主要是减少的。结果还表明，对重组自身抗原反应的T细胞在胸腺瘤和血液中存在T细胞，而T细胞对外来抗原（即破伤风环形体）的反应仅见于循环T细胞，而不见于胸腺瘤衍生的T细胞。这些功能研究支持了胸腺瘤内发生的胸腺生成改变外周T细胞库的假设。由于许多胸腺瘤富含自身抗原特异性 T 细胞，肿瘤内 T 细胞输出导致的循环 T 细胞亚群组成的紊乱可能导致胸腺瘤患者出现副肿瘤性自身免疫性疾病。 (C) 2000 年，美国血液学会。
Thymomas are the only tumors that are proven to generate mature T cells from immature precursors. It is unknown, however, whether intratumorous thymopoiesis has an impact on the peripheral T-cell pool and might thus be related to the high frequency of thymoma-associated myasthenia gravis, This study shows, using fluorescence-activated cell sortingbased analyses and T-cell proliferation assays, that thymopoiesis and T-cell function in thymomas correspond with immunologic alterations in the blood. Specifically, the proportion of circulating CD45RA(+)CD8(+) T cells is significantly increased in patients with thymoma compared with normal controls, in accordance with intratumorous T-cell development that is abnormally skewed toward the CD8(+) phenotype, Moreover, it is primarily the proportion of circulating CD45RA(+)CD8(+) T cells that decreases after thymectomy, The results also demonstrate that T cells reactive toward recombinant autoantigens are distributed equally between thymomas and blood, whereas T-cell responses to foreign antigen (ie, tetanus toroid) are seen only among circulating T cells and not among thymoma-derived T cells, These functional studies support the hypothesis that thymopoiesis occurring within thymomas alters the peripheral T-cell repertoire. Because many thymomas are enriched with autoantigen-specific T cells, a disturbance of circulating T-cell subset composition by export of intratumorous T cells may contribute to paraneoplastic autoimmune disease arising in patients with thymoma. (C) 2000 by The American Society of Hematology.