Lymphoid hyperplasia, CD45RBhigh to CD45RBlow T-cell imbalance, and suppression of Type I diabetes mellitus result from TNF blockade in NOD-->NOD-scid adoptive T cell transfer.
Lymphoid hyperplasia, CD45RBhigh to CD45RBlow T-cell imbalance, and suppression of Type I diabetes mellitus result from TNF blockade in NOD-->NOD-scid adoptive T cell transfer.
复制标题
淋巴增生、CD45RBhigh 到 CD45RBlow T 细胞失衡以及 I 型糖尿病的抑制是由于 NOD-->NOD-scid 过继性 T 细胞转移中 TNF 阻断所致。
DOI：
10.1007/s001250051097
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发表时间：
1998
期刊：
影响因子：
8.2
通讯作者：
Beutler,B
中科院分区：
文献类型：
--
作者：
Brown,GR;Silva,MD;Thompson,PA;Beutler,B
抗体介导的肿瘤坏死因子 (TNF) 活性的持续抑制可以为非肥胖糖尿病 (NOD) 小鼠提供针对 I 型（胰岛素依赖性）糖尿病的保护。然而，这种效应的机制仍不清楚：TNFα可能是针对胰岛抗原产生特异性免疫反应所必需的，或者它可能直接参与β细胞的破坏。在这项研究中，通过转移 NOD 脾 T 细胞诱导糖尿病，在 NOD 严重联合免疫缺陷 (scid) 小鼠中启动了 β 细胞的自身免疫破坏。 TNFα 活性的阻断是在转移后的很短的时间内实现的。 TNFα 的瞬时抑制大大降低了糖尿病前期 NOD 脾细胞受体的胰岛淋巴细胞数量和糖尿病发病率。保护作用超出了有效 TNF 阻断的时间间隔。此外，只有从 6 周大的捐赠者处获得细胞时才能观察到保护作用。在过继转移的情况下，自身免疫的抑制是可逆的，如脾细胞从主要受体转移到第二个 NOD-scidhost 导致糖尿病结果所表明的。 TNFα 的阻断伴随着脾脏大小的显着增加和脾细胞总数的翻倍，这表明 TNFα 通常可能消除受体内移植的 T 细胞亚群。进一步分析显示，CD4 + T 细胞绝对计数增加，CD45RBhigh 与 CD45RBlow 比率明显扭曲，脾脏中 CD45RBlow 计数相对增加。 TNFα 似乎可以调节移植 T 细胞群的数量和亚型分布。 [糖尿病学（1998）41：1502–1510]
Sustained antibody-mediated inhibition of tumor necrosis factor (TNF) activity offers protection against Type I (insulin-dependent) diabetes mellitus in non-obese diabetic (NOD) mice. The mechanism of this effect, however, has remained obscure: TNFα might be required for the development of specific immune responses to islet antigens or it could directly participate in destruction of beta cells. In this study, autoimmune destruction of beta cells was initiated in NOD-severe combined immunodeficient (scid) mice by transfer of NOD splenic T-cells to induce diabetes. The blockade of TNFα activity was achieved during a narrow window of time after transfer. Transient inhibition of TNFα greatly reduced the number of islet lymphocytes and the incidence of diabetes in recipients of prediabetic NOD spleen cells. Protection extended beyond the interval of effective TNF blockade. Furthermore, the protective effect was only observed if cells were obtained from 6-week-old donors. The suppression of autoimmunity was reversible in the context of adoptive transfer as indicated by the transfer of splenocytes from the primary recipient to a second NOD-scidhost led to a diabetic outcome. The blockade of TNFα was accompanied by a considerable increase in spleen size and doubling of the total splenocyte count, suggesting that TNFα might normally eliminate a transplanted T-cell subset within the recipients. Further analysis showed an increase in the absolute count of CD4 + T cells and pronounced distortion of the CD45RBhighto CD45RBlowratio, with a relative augmentation in the CD45RBlowcount in the spleen. TNFα appears to regulate the number and subtype distribution of a transplanted T cell population. [Diabetologia (1998) 41: 1502–1510]