Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3.
Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3.
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DOI：
10.4049/jimmunol.1100714
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发表时间：
2011-10-01
期刊：
影响因子：
--
通讯作者：
Vignali DA
中科院分区：
文献类型：
--
作者：
Bettini M;Szymczak-Workman AL;Forbes K;Castellaw AH;Selby M;Pan X;Drake CG;Korman AJ;Vignali DA
LAG-3（CD 223）是最大调节性T细胞功能和控制CD 4+和CD 8 + T细胞稳态所需的CD 4同源物。Lag 3 −/− NOD小鼠发生糖尿病的速度大大加快，发病率为100%。连续转移实验表明，LAG-3主要负责限制CD 4 + T细胞的致病潜力，并在较小程度上限制CD 8 + T细胞。Lag 3 −/−小鼠表现出加速的侵袭性胰岛炎，对应于增加的CD 4+和CD 8 + T细胞胰岛浸润和胰岛内增殖。胰岛抗原反应性嗜铬粒蛋白A特异性CD 4 + T细胞和IGRP特异性CD 8 + T细胞的频率在Lag 3 −/−小鼠的胰岛中显著增加，这表明通常受LAG-3抑制的致病性克隆的早期扩增。我们得出结论，LAG-3是必要的调节CD 4+和CD 8 + T细胞功能在自身免疫性糖尿病，因此可能有助于限制自身免疫性疾病的环境。
LAG-3 (CD223) is a CD4 homolog that is required for maximal regulatory T cell function and for the control of CD4+ and CD8+ T cell homeostasis. Lag3−/− NOD mice developed substantially accelerated diabetes with 100% incidence. Adoptive transfer experiments revealed that LAG-3 was primarily responsible for limiting the pathogenic potential of CD4+ T cells, and to a lesser extent CD8+ T cells. Lag3−/− mice exhibited accelerated, invasive insulitis, corresponding to increased CD4+ and CD8+ T cell islet infiltration and intra-islet proliferation. The frequencies of islet antigen reactive chromogranin A-specific CD4+ T cells and IGRP-specific CD8+ T cells were significantly increased in the islets of Lag3−/− mice, suggesting an early expansion of pathogenic clones which is normally restrained by LAG-3. We conclude that LAG-3 is necessary for regulating CD4+ and CD8+ T cell function during autoimmune diabetes, and thus may contribute to limiting autoimmunity in disease-prone environments.
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影响因子：
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