Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process.
Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process.
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肿瘤坏死因子α对NOD小鼠胰岛素依赖性糖尿病的影响。 I.自身免疫和糖尿病生成过程的早期发展。
DOI：
10.1084/jem.180.3.995
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发表时间：
1994-09-01
影响因子：
15.3
通讯作者：
McDevitt, Hugh O.
中科院分区：
文献类型：
--
作者：
Yang, Xiao-Dong;Tisch, Roland;Singer, Steven M.;Cao, Zhu A.;Liblau, Roland S.;Schreiber, Robert D.;McDevitt, Hugh O.
肿瘤坏死因子(TNF) α是一种具有强大免疫调节功能的细胞因子。为了评估这种细胞因子在自身免疫早期发展中的潜在作用，我们研究了TNF对非肥胖糖尿病（NOD）小鼠胰岛素依赖型糖尿病（IDDM）发展的影响，NOD是一种自身免疫性胰岛素依赖型糖尿病的自发小鼠模型。每隔一天用TNF治疗新生雌性NOD小鼠3周，导致疾病发病较早（对照组小鼠为10周，对照组小鼠为15周），20周龄前发病率为100%（对照组磷酸盐缓冲盐水治疗的雌性小鼠为20周龄时的45%）。相反，给予抗tnf单克隆抗体TN3.19.12可完全预防IDDM。体外增殖试验表明，用TNF处理的小鼠对一组β细胞自身抗原产生了增加的T细胞反应，而抗TNF处理导致对自身抗原无反应。此外，自身抗体对β细胞抗原的反应与T细胞的反应是平行的。TNF介导的作用似乎高度依赖于年龄。对出生或2周龄的动物进行治疗也有类似的效果。然而，如果在4周龄时开始治疗，TNF会延迟疾病的发作。这些数据表明，TNF在β -胰岛细胞自身免疫的早期发展中具有关键作用。
Tumor necrosis factor (TNF) alpha is a cytokine that has potent immune regulatory functions. To assess the potential role of this cytokine in the early development of autoimmunity, we investigated the effect of TNF on the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice, a spontaneous murine model for autoimmune, insulin-dependent type I diabetes. Treatment of newborn female NOD mice with TNF every other day for 3 wk, led to an earlier onset of disease (10 versus 15 wk of age in control mice) and 100% incidence before 20 wk of age (compared to 45% at 20 wk of age in control phosphate-buffered saline treated female mice). In contrast, administration of an anti-TNF monoclonal antibody, TN3.19.12, resulted in complete prevention of IDDM. In vitro proliferation assays demonstrated that mice treated with TNF developed an increased T cell response to a panel of beta cell autoantigens, whereas anti-TNF treatment resulted in unresponsiveness to the autoantigens. In addition, autoantibody responses to the panel of beta cell antigens paralleled the T cell responses. The effects mediated by TNF appear to be highly age dependent. Treatment of animals either from birth or from 2 wk of age had a similar effect. However, if treatment was initiated at 4 wk of age, TNF delayed disease onset. These data suggest that TNF has a critical role in the early development of autoimmunity towards beta-islet cells.
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影响因子：
15.9
作者：
HANNINEN, A;TAYLOR, C;MICHIE, SA
通讯作者：
MICHIE, SA
DOI：
10.1016/0090-1229(92)90215-a
发表时间：
1992-11-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
LAPCHAK, PH;GUILBERT, LJ;RABINOVITCH, A
通讯作者：
RABINOVITCH, A
影响因子：
7.7
作者：
CHARLTON, B;MANDEL, TE
通讯作者：
MANDEL, TE
影响因子：
5.4
作者：
DARDENNE, M;LEPAULT, F;BACH, JF
通讯作者：
BACH, JF
影响因子：
64.8
作者：
HUTCHINGS, P;ROSEN, H;COOKE, A
通讯作者：
COOKE, A