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首页> 外文期刊>Developmental immunology >Evidence for distinct mechanisms in the shaping of the CD4 T cell repertoire in histologically distinct myasthenia gravis-associated thymomas.
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Evidence for distinct mechanisms in the shaping of the CD4 T cell repertoire in histologically distinct myasthenia gravis-associated thymomas.

机译：在组织学上不同的重症肌无力相关胸腺瘤中，CD4 T细胞库形成的不同机制的证据。

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摘要

The major histocompatibility complex (MHC) class II is involved both in thymocyte maturation and peptide presentation and might thus play a key role in the pathogenesis of paraneoplastic myasthenia gravis (MG) in thymomas. To further investigate this issue, we analyzed and scored the expression of epithelial class II expression in 35 thymomas (medullary, MDT; mixed, MXT; cortical and well differentiated thymic carcinoma, CT/WDTC) and correlated it with the histological tumor subtype, prevalence of MG and thymocyte maturation, which was analyzed by flow cytometry and RT-PCR. Our results show that both MHC class II expression and thymocyte maturation are highly dependent on the histological tumor subtype. CT/WDTC retain features of the normal outer thymic cortex, namely substantial MHC class II expression together with normal early thymocyte maturation until late phases of positive selection, but disturbed terminal thymopoiesis. By contrast, MDT and MXT retain features of the normal inner cortex and the medulla with low to absent class II expression and highly abnormal early thymocyte maturation including impaired positive selection, while terminal T cell maturation in MXT appeared undisturbed. There was no correlation between MHC class II expression and MG status for a given tumor subtype. In conclusion, our results provide evidence for a different histogenesis of cortical thymomas and well differentiated carcinomas on the one hand and mixed and medullary thymomas on the other. Decreased expression levels of MHC class II, although of crucial importance for abnormal intratumorous maturation, are not sufficient to explain the emergence of paraneoplastic MG.
机译：II类主要组织相容性复合物（MHC）参与胸腺细胞成熟和肽呈递，因此可能在胸腺瘤的副肿瘤性重症肌无力（MG）的发病机理中起关键作用。为了进一步研究该问题，我们分析了35种胸腺瘤（髓样，MDT，混合型，MXT，皮质和高分化胸腺癌，CT / WDTC）中上皮II类表达的表达并进行了评分，并将其与组织学肿瘤亚型，患病率相关MG和胸腺细胞的成熟，通过流式细胞术和RT-PCR进行分析。我们的结果表明，MHC II类表达和胸腺细胞成熟都高度依赖于组织学肿瘤亚型。 CT / WDTC保留了正常的胸腺外皮层的特征，即大量的MHC II类表达以及正常的早期胸腺细胞成熟直至阳性选择的晚期，但扰乱了末期胸腺造血功能。相比之下，MDT和MXT保留了正常内皮层和髓质的特征，具有低至无II类表达和高度异常的早期胸腺细胞成熟，包括阳性选择受损，而MXT中的终末T细胞成熟似乎不受干扰。对于给定的肿瘤亚型，MHC II类表达与MG状态之间没有相关性。总之，我们的结果提供了证据，一方面显示了皮质胸腺瘤和分化良好的癌，另一方面出现了混合型和延髓性胸腺瘤的不同组织发生。 MHC II类表达水平的降低，尽管对于异常肿瘤内成熟至关重要，但不足以解释副肿瘤性MG的出现。

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