CD4+ T cell depletion, immune activation and increased production of regulatory T cells in the thymus of HIV-infected individuals.
CD4+ T cell depletion, immune activation and increased production of regulatory T cells in the thymus of HIV-infected individuals.
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DOI：
10.1371/journal.pone.0010788
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发表时间：
2010-05-24
期刊：
影响因子：
3.7
通讯作者：
Gori A
中科院分区：
文献类型：
--
作者：
Bandera A;Ferrario G;Saresella M;Marventano I;Soria A;Zanini F;Sabbatini F;Airoldi M;Marchetti G;Franzetti F;Trabattoni D;Clerici M;Gori A
HIV影响胸腺的机制是多方面的，而且只有一部分人知道，胸腺功能障碍在HIV/AIDS免疫发病机制中的作用仍然知之甚少。为了评估HIV感染对HIV感染者胸腺内T细胞前体细胞的影响，我们对7例HIV感染者和10例HIV阴性成人心脏手术后胸腺组织进行了详细的免疫表型研究。我们发现，HIV感染者的胸腺以相对缺乏的CD4+单一阳性T细胞和相对丰富的CD8+单一阳性T细胞为特征。此外，来自HIV感染者的胸腺细胞表现出激活和增殖细胞水平的增加。我们的分析还显示，在HIV感染者的早期胸腺细胞中，白细胞介素7受体的表达减少，而在成熟的双阳性和单阳性细胞中，同样的表达增加。在HIV感染的胸腺中，调节性T细胞(CD25+FoxP3+)的频率显著增加，特别是在预先承诺的CD4单一阳性细胞中。我们的数据提示，HIV感染与胸腺细胞免疫表型的一系列复杂变化有关，包括胸腺内CD4+T细胞前体细胞减少，活化标志物表达增加，IL-7R表达模式改变和T调节细胞生成丰富。
Mechanisms by which HIV affects the thymus are multiple and only partially known, and the role of thymic dysfunction in HIV/AIDS immunopathogenesis remains poorly understood. To evaluate the effects of HIV infection on intra-thymic precursors of T cells in HIV-infected adults, we conducted a detailed immunophenotypic study of thymic tissue isolated from 7 HIV-infected and 10 HIV-negative adults who were to undergo heart surgery. We found that thymuses of HIV-infected individuals were characterized by a relative depletion of CD4+ single positive T cells and a corresponding enrichment of CD8+ single positive T cells. In addition, thymocytes derived from HIV-infected subjects showed increased levels of activated and proliferating cells. Our analysis also revealed a decreased expression of interleukin-7 receptor in early thymocytes from HIV-infected individuals, along with an increase in this same expression in mature double- and single-positive cells. Frequency of regulatory T cells (CD25+FoxP3+) was significantly increased in HIV-infected thymuses, particularly in priorly-committed CD4 single positive cells. Our data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4+ T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation.
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影响因子：
4.4
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