Deficiency in NOD antigen-presenting cell function may be responsible for suboptimal CD4+ CD25+ T-cell-mediated regulation and type 1 diabetes development in NOD mice
Deficiency in NOD antigen-presenting cell function may be responsible for suboptimal CD4+ CD25+ T-cell-mediated regulation and type 1 diabetes development in NOD mice
复制标题
DOI：
10.2337/db05-0810
复制
发表时间：
2006-07-01
期刊：
影响因子：
7.7
通讯作者：
Kosiewicz, Michele M.
中科院分区：
文献类型：
--
作者：
Alard, Pascale;Manirarora, Jean N.;Kosiewicz, Michele M.
抗原呈递细胞（APC）和T细胞（包括调节细胞）的各种缺陷与NOD小鼠的1型糖尿病发展相关。CD 4（+）CD 25（+）调节细胞在控制各种自身免疫性疾病中起着至关重要的作用，其数量或功能的缺陷可能参与疾病的发展。目前的研究表明，NOD小鼠有较少的CD 4（+）CD 25（+）调节细胞，表达正常水平的糖皮质激素诱导的肿瘤坏死因子受体和细胞毒性T淋巴细胞相关抗原-4。我们还发现，与B6 APC刺激的B6 CD 4（+）CD 25（+）细胞相比，NOD CD 4（+）CD 25（+）细胞在体外用抗CD 3和NOD APC刺激后调节较差。令人惊讶的是，用B6 APC刺激NOD CD 4 + CD 25+细胞恢复了调节，而用相反的组合，NOD APC不能正确地激活B6 CD 4（+）CD 25（+）细胞。有趣的是，来自无病（> 30周龄）但非糖尿病的NOD小鼠的APC能够在体外和体内激活CD 4（+）CD 25（+）调节功能，因为只有无病NOD小鼠的脾脏含有有效的CD 4（+）CD 25（+）调节细胞，当转移到年轻的NOD受体时，这些细胞可以防止疾病的发展。这些数据表明，NOD APC未能激活CD 4（+）CD 25（+）调节细胞可能在控制NOD小鼠1型糖尿病的发展中发挥重要作用。
Various defects in antigen-presenting cells (APCs) and T-cells, including regulatory cells, have been associated with type 1 diabetes development in NOD mice. CD4(+)CD25(+) regulatory cells play a crucial role in controlling various autoimmune diseases, and a deficiency in their number or function could be involved in disease development. The current study shows that NOD mice had fewer CD4(+)CD25(+) regulatory cells, which expressed normal levels of glucocorticoid-induced tumor necrosis factor receptor and cytotoxic T-lymphocyte-associated antigen-4. We have also found that NOD CD4(+)CD25(+) cells regulate poorly in vitro after stimulation with anti-CD3 and NOD APCs in comparison with B6 CD4(+)CD25(+) cells stimulated with B6 APCs. Surprisingly, stimulation of NOD CD4+CD25+ cells with B6 APCs restored regulation, whereas with the reciprocal combination, NOD APCs failed to activate B6 CD4(+)CD25(+) cells properly. Interestingly, APCs from disease-free (> 30 weeks of age), but not diabetic, NOD mice were able to activate CD4(+)CD25(+) regulatory function in vitro and apparently in vivo because only spleens of disease-free NOD mice contained potent CD4(+)CD25(+) regulatory cells that prevented disease development when transferred into young NOD recipients. These data suggest that the failure of NOD APCs to activate CD4(+)CD25(+) regulatory cells may play an important role in controlling type 1 diabetes development in NOD mice.