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雄性大鼠胸腺细胞上CD90表达及胸腺细胞成熟过程中TCR依赖阶段的年龄相关变化。

Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats.

作者信息

Leposavić Gordana, Pesić Vesna, Kosec Dusko, Radojević Katarina, Arsenović-Ranin Nevena, Pilipović Ivan, Perisić Milica, Plećas-Solarović Bosiljka

机构信息

Institute of Immunology and Virology Torlak, Immunology Research Center Branislav Janković, Belgrade, Serbia and Montenegro.

出版信息

Exp Gerontol. 2006 Jun;41(6):574-89. doi: 10.1016/j.exger.2006.03.006. Epub 2006 May 2.

Abstract

To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCRalphabeta and (ii) Thy-1, which is supposed to be a regulator of TCRalphabeta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCRalphabeta signalling in the development of CD4+25+T(reg)-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRalphabeta-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCRalphabeta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCRalphabeta(high) to the SP TCRalphabeta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T(reg)-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing.

摘要

为阐明衰老对T细胞成熟的影响,我们分析了3月龄和18月龄大鼠中以下指标的表达:(i) CD4/CD8/TCRαβ和(ii) Thy-1,后者被认为是TCRαβ信号的调节因子,从而也是胸腺细胞选择阈值的调节因子。由于TCRαβ信号在CD4+25+T(reg)细胞发育中起着重要作用,因此我们也对这些细胞的频率进行了定量分析。我们证明,与小鼠一样,CD4-8-双阴性(DN)发育阶段的早期胸腺细胞分化步骤对年龄敏感。此外,我们发现T细胞发育中依赖TCRαβ的阶段受到衰老的影响,这很可能是由于进入选择过程的TCRαβ(low)胸腺细胞上Thy-1表达受损所致。老年大鼠中选择后CD4+8+双阳性(DP)细胞的频率降低,以及成熟单阳性(SP)细胞的比例过高,很可能表明从DP TCRαβ(high)到SP TCRαβ(high)发育阶段的分化过渡更有效,随后成熟SP细胞迁移前的增殖增加。此外,该研究表明老年大鼠胸腺内CD4+25+T(reg)细胞的生成受损,从而为衰老过程中自身免疫性疾病频率增加提供了一种可能的解释。

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