Altered CD161bright CD8+ Mucosal Associated Invariant T (MAIT)-Like Cell Dynamics and Increased Differentiation States among Juvenile Type 1 Diabetics
Altered CD161bright CD8+ Mucosal Associated Invariant T (MAIT)-Like Cell Dynamics and Increased Differentiation States among Juvenile Type 1 Diabetics
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DOI：
10.1371/journal.pone.0117335
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发表时间：
2015-01-27
期刊：
影响因子：
3.7
通讯作者：
Sarvetnick, Nora E.
中科院分区：
文献类型：
--
作者：
Harms, Robert Z.;Lorenzo, Kristina M.;Sarvetnick, Nora E.
1A型糖尿病（T1D）被认为是由免疫介导的β细胞破坏引起的，但T1D的免疫学基础仍有争议。微生物多样性促进某些免疫亚群的成熟和激活，包括CD161（明亮）CD8（+）粘膜相关不变T （MAIT）细胞，并且在1型糖尿病患者（T1Ds）中报道了肠道粘膜反应的改变。我们分析了青少年T1Ds和健康对照者外周血白细胞中的T细胞群。我们发现，在T1Ds和对照组之间，MAIT细胞的比例和绝对数量相似。此外，在健康对照组中，MAIT细胞比例随着年龄的增长而增加，但在长期t1d患者中没有观察到这种趋势。此外，CD27-MAIT细胞亚群在T1Ds中显著增加，并与HbA1c水平呈正相关。然而，在t1d按年龄分层后，与年龄匹配的对照组相比，年轻组CD27-MAIT细胞的比例显着增加，并且这种比例增加似乎与HbA1c水平无关。最后，我们分析了CD27-MAIT细胞的功能，并观察到与CD27(+) MAIT细胞相比，CD27细胞中IL-17A的产生增加。总的来说，我们的数据揭示了t1d和对照组之间不同的MAIT细胞动力学，以及t1d中MAIT细胞激活增加的迹象。这些变化可能与t1d患者的高血糖和黏膜挑战增加有关。
Type 1A diabetes (T1D) is believed to be caused by immune-mediated destruction of beta-cells, but the immunological basis for T1D remains controversial. Microbial diversity promotes the maturation and activation of certain immune subsets, including CD161(bright) CD8(+) mucosal associated invariant T (MAIT) cells, and alterations in gut mucosal responses have been reported in type 1 diabetics (T1Ds). We analyzed T cell populations in peripheral blood leukocytes from juvenile T1Ds and healthy controls. We found that proportion and absolute number of MAIT cells were similar between T1Ds and controls. Furthermore, while MAIT cell proportions increased with age among healthy controls, this trend was not observed among long-standing T1Ds. Additionally, the CD27-MAIT cell subset is significantly increased in T1Ds and positively correlated with HbA1c levels. However, after T1Ds are stratified by age, the younger group has significantly increased proportions of CD27-MAIT cells compared to age-matched controls, and this proportional increase appears to be independent of HbA1c levels. Finally, we analyzed function of the CD27-MAIT cells and observed that IL-17A production is increased in CD27-compared to CD27(+) MAIT cells. Overall, our data reveal disparate MAIT cell dynamics between T1Ds and controls, as well as signs of increased MAIT cell activation in T1Ds. These changes may be linked to hyperglycemia and increased mucosal challenge among T1Ds.