Tumor necrosis factor-a regulation of CD4+C25+ T cell levels in NOD mice
Tumor necrosis factor-a regulation of CD4+C25+ T cell levels in NOD mice
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DOI：
10.1073/pnas.172382999
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发表时间：
2002-09-17
影响因子：
11.1
通讯作者：
McDevitt, HO
中科院分区：
文献类型：
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作者：
Wu, AJ;Hua, H;McDevitt, HO
肿瘤坏死因子- α (TNF)在非肥胖糖尿病（NOD）小鼠中差异调节I型糖尿病的机制尚不清楚。CD4(+)CD25(+) T细胞被认为是自我耐受的介质。我们发现(i) NOD小鼠胸腺和脾脏中CD4+CD25+ T细胞相对缺乏；(1)给NOD小鼠施用TNF或抗TNF可以调节这一群体的水平，这与他们观察到的NOD小鼠糖尿病的年龄依赖性差异效应一致；（iii）新生儿用TNF治疗NOD小鼠的CD4(+)CD25(+) T细胞在转移系统中的效应功能受损，而新生儿用抗TNF治疗的小鼠在预防糖尿病的能力方面没有改变；（iv）向新生NOD小鼠反复注射CD4(+)CD25(+) T细胞，只要补充了，就会延迟糖尿病的发生。这些数据表明，CD4(+)CD25(+) T细胞数量和功能的改变可能是TNF和抗TNF调节NOD小鼠I型糖尿病的一个机制。
The mechanism by which tumor necrosis factor-alpha (TNF) differentially modulates type I diabetes mellitus in the nonobese diabetic (NOD) mouse is not well understood. CD4(+)CD25(+) T cells have been implicated as mediators of self-tolerance. We show (i) NOD mice have a relative deficiency of CD4+CD25+ T cells in thymus and spleen; (it) administration of TNF or anti-TNF to NOD mice can modulate levels of this population consistent with their observed differential age-dependent effects on diabetes in the NOD mouse; (iii) CD4(+)CD25(+) T cells from NOD mice treated neonatally with TNF show compromised effector function in a transfer system, whereas those treated neonatally with anti-TNF show no alteration in ability to prevent diabetes; and (iv) repeated injection of CD4(+)CD25(+) T cells into neonatal NOD mice delays diabetes onset for as long as supplementation occurred. These data suggest that alterations in the number and function of CD4(+)CD25(+) T cells may be one mechanism by which TNF and anti-TNF modulate type I diabetes mellitus in NOD mice.