Immunological tolerance to a pancreatic antigen as a result of local expression of TNF alpha by islet beta cells
Immunological tolerance to a pancreatic antigen as a result of local expression of TNF alpha by islet beta cells
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DOI：
10.1016/s1074-7613(00)80361-1
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发表时间：
1997-09-01
期刊：
影响因子：
32.4
通讯作者：
Glaichenhaus, N
中科院分区：
文献类型：
--
作者：
McSorley, SJ;Soldera, S;Glaichenhaus, N
最近的实验表明，肿瘤坏死因子α（TNF α）可以下调胰岛特异性T细胞，防止自身免疫性糖尿病的发展。在这里，我们证明了在胰腺中表达TNF α和主要利什曼原虫LACK抗原的转基因小鼠（RIP-TNF α/RIP-LACK）表现出对LACK的CD 4（+）T细胞应答能力受损。此外，TCR转基因小鼠（TCR-LACK/RIP-TNF α/RIP-LACK）的外周血CD 4（+）T细胞在体外对LACK肽产生的白细胞介素-2减少，但辅助性T细胞因子2水平升高。总之，我们的数据表明，TNF α可能在体内通过诱导对胰腺抗原的耐受来调节潜在的损伤性自身反应性T细胞应答。
Recent experiments have suggested that tumor necrosis factor alpha (TNF alpha) can down-regulate islet-specific T cells and prevent the development of autoimmune diabetes. Here we demonstrate that transgenic mice expressing both TNF alpha and the Leishmania major LACK antigen in the pancreas (RIP-TNF alpha/RIP-LACK) exhibit an impaired ability to mount a CD4(+) T cell response against LACK. In addition, peripheral CD4(+) T cells from TCR transgenic mice (TCR-LACK/RIP-TNF alpha/RIP-LACK) produced reduced interleukin-2 but elevated levels of T helper 2 cytokines in response to LACK peptide in vitro. Taken together, our data suggest that TNF alpha may act in vivo to modulate a potentially damaging self-reactive T cell response by inducing tolerance to pancreatic antigens.