Marwaha Ashish K, Crome Sarah Q, Panagiotopoulos Constadina, Berg Kyra B, Qin Huilian, Ouyang Qin, Xu Lixin, Priatel John J, Levings Megan K, Tan Rusung
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
J Immunol. 2010 Oct 1;185(7):3814-8. doi: 10.4049/jimmunol.1001860. Epub 2010 Sep 1.
CD4(+)FOXP3(+) regulatory T cells are essential for immune tolerance, and murine studies suggest that their dysfunction can lead to type 1 diabetes (T1D). Human studies assessing regulatory T cell dysfunction in T1D have relied on analysis of FOXP3-expressing cells. Recently, distinct subsets of CD4(+)FOXP3(+) T cells with differing function were identified. Notably, CD45RA(-)CD25(int)FOXP3(low) T cells lack suppressive function and secrete the proinflammatory cytokine IL-17. Therefore, we evaluated whether the relative fractions of CD4(+)FOXP3(+) subsets are altered in new-onset T1D subjects. We report that children with new-onset T1D have an increased proportion of CD45RA(-)CD25(int)FOXP3(low) cells that are not suppressive and secrete significantly more IL-17 than other FOXP3(+) subsets. Moreover, these T1D subjects had a higher proportion of both CD4(+) and CD8(+) T cells that secrete IL-17. The bias toward IL-17-secreting T cells in T1D suggests a role for this proinflammatory cytokine in the pathogenesis of disease.
CD4(+)FOXP3(+)调节性T细胞对免疫耐受至关重要，小鼠研究表明其功能障碍可导致1型糖尿病（T1D）。评估T1D中调节性T细胞功能障碍的人体研究依赖于对表达FOXP3的细胞进行分析。最近，已鉴定出具有不同功能的CD4(+)FOXP3(+)T细胞的不同亚群。值得注意的是，CD45RA(-)CD25(int)FOXP3(low)T细胞缺乏抑制功能并分泌促炎细胞因子IL-17。因此，我们评估了新发T1D受试者中CD4(+)FOXP3(+)亚群的相对比例是否发生改变。我们报告称，新发T1D儿童中不具有抑制功能且分泌IL-17显著多于其他FOXP3(+)亚群的CD45RA(-)CD25(int)FOXP3(low)细胞比例增加。此外，这些T1D受试者中分泌IL-17的CD4(+)和CD8(+)T细胞比例更高。T1D中向分泌IL-17的T细胞的偏向表明这种促炎细胞因子在疾病发病机制中起作用。
