CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose
CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose
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DOI：
10.1073/pnas.96.22.12703
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发表时间：
1999-10-26
影响因子：
11.1
通讯作者：
Heath, WR
中科院分区：
文献类型：
--
作者：
Kurts, C;Sutherland, RM;Heath, WR
据报道，有两种主要机制可以防止胰岛特异性CD8+T细胞的自身反应：无知和耐受。当无知起作用时，幼稚的自身反应性CD8+T细胞会忽略胰岛抗原并进行再循环而不会造成损害，除非被外部刺激激活。在耐受的情况下，CD8(+) T 细胞被删除。哪些因素会影响每个特定的结果，以前是未知的。在这里，我们证明自身抗原的浓度决定了哪种机制起作用。当卵清蛋白（OVA）在转基因小鼠的胰岛中以相对较低的浓度表达时，没有可检测到的交叉呈递，并且CD8（+）T细胞区室仍然不了解OVA。在表达较高剂量 OVA 的小鼠中，可检测到交叉呈递并导致 OVA 特异性 CD8(+) T 细胞外周缺失。当通过用不能呈递 OVA 的细胞重建骨髓室来阻止交叉呈递时，缺失耐受就会转化为无知。因此，免疫系统使用两种策略来避免CD8+T细胞介导的自身免疫：对于高剂量抗原，它删除自身反应性T细胞，而对于低剂量抗原，它依赖于无知。
There are two major mechanisms reported to prevent the autoreactivity of islet-specific CD8(+) T cells: ignorance and tolerance. When ignorance is operative, naive autoreactive CD8(+) T cells ignore islet antigens and recirculate without causing damage, unless activated by an external stimulus. In the case of tolerance, CD8(+) T cells are deleted. Which factor(s) contributes to each particular outcome was previously unknown. Here, we demonstrate that the concentration of self antigen determines which mechanism operates. When ovalbumin (OVA) was expressed at a relatively low concentration in the pancreatic islets of transgenic mice, there was no detectable cross-presentation, and the CD8(+) T cell compartment remained ignorant of OVA. In mice expressing higher doses of OVA, cross-presentation was detectable and led to peripheral deletion of OVA-specific CD8(+) T cells. When cross-presentation was prevented by reconstituting the bone marrow compartment with cells incapable of presenting OVA, deletional tolerance was converted to ignorance. Thus, the immune system uses two strategies to avoid CD8(+) T cell-mediated autoimmunity: for high dose antigens, it deletes autoreactive T cells, whereas for lower dose antigens, it relies on ignorance.