Thymopoiesis, Regulatory T Cells, and TCRVβ Expression in Thymoma With and Without Myasthenia Gravis, and Modulatory Effects of Steroid Therapy
Thymopoiesis, Regulatory T Cells, and TCRVβ Expression in Thymoma With and Without Myasthenia Gravis, and Modulatory Effects of Steroid Therapy
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DOI：
10.1007/s10875-007-9147-2
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发表时间：
2008-03
影响因子：
9.1
通讯作者：
A. Fattorossi;A. Battaglia;Alexia Buzzonetti;G. Minicuci;Raffaella Riso;L. Peri;G. Scambia;A. Evoli
中科院分区：
文献类型：
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作者：
A. Fattorossi;A. Battaglia;Alexia Buzzonetti;G. Minicuci;Raffaella Riso;L. Peri;G. Scambia;A. Evoli
我们分析了胸腺瘤伴和不伴重症肌无力（MG，MG-胸腺瘤，非MG-胸腺瘤）和MG相关非肿瘤性胸腺（MG-NNT）中胸腺细胞和胸腺调节性T细胞（CD 4SPCD 25 + Foxp 3+细胞，Treg）的发育。在MG-和非MG-胸腺瘤中均观察到通过CD 4 + CD 8+向CD 4 + CD 8 −转变的未成熟CD 4 + CD 8 − CD 3 −胸腺细胞数量增加，以及通过CD 4 + CD 8+向CD 4 − CD 8+转变的T细胞受体Vβ（TCRVβ）发育异常。终末胸腺生成，即，CD 4 + CD 8 − CD 3+和CD 8 + CD 4 − CD 3+亚群中的CD 45 RA+细胞在MG-胸腺瘤中偏向于CD 4+区室，在非MG-胸腺瘤中偏向于CD 8+区室，但胸腺输出仅在后者中增加，这与CD 8+淋巴细胞可能在自身致敏的初始阶段起作用的假设一致，与副肿瘤性MG中CD 4 +T淋巴细胞输出增加的相关性不一致。正常胸腺和MG-NNT以及MG-和非MG-胸腺瘤中的Treg水平相似，胸腺瘤中Treg细胞中的TCRVβ发育轻微改变，但与MG存在无关。因此，MG背景下缺陷性Treg发育的相关性仍有待确定。大多数胸腺生成的改变都可以通过治疗性皮质类固醇给药来纠正，并且类固醇给药的影响可能是由胸腺微环境介导的。
We analyzed thymocyte and thymic regulatory T cell (CD4SPCD25+Foxp3+cells, Treg) development in thymoma with and without myasthenia gravis (MG, MG-thymoma, non-MG-thymoma) and in MG-associated non-neoplastic thymus (MG-NNT). An increased number of immature CD4+CD8−CD3−thymocytes through the CD4+CD8+to CD4+CD8−transition and an abnormal T cell receptor Vβ (TCRVβ) development through the CD4+CD8+to CD4−CD8+transition were seen both in MG-and non-MG-thymomas. Terminal thymopoiesis, i.e., CD45RA+cells within the CD4+CD8−CD3+and CD8+CD4−CD3+subsets, was skewed towards the CD4+compartment in MG-thymoma and CD8+compartment in non-MG-thymoma, but thymic export was increased only in the latter in keeping with the hypothesis that CD8+lymphocytes may play a role in the initial stages of autosensitization and in disagreement with the relevance of an increased output of CD4+T lymphocytes in paraneoplastic MG. Treg level in normal thymus and MG-NNT and both MG- and non-MG-thymoma was similar, and TCRVβ development in Treg cells was slightly altered in thymoma but irrespective of MG presence. Thus, the relevance of a defective Treg development in MG context remains to be established. Most alterations in thymopoiesis were corrected by therapeutic corticosteroid administration, and the effects of steroid administration may be mediated by thymic microenvironment.