A range of CD4 T cell tolerance: Partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis
A range of CD4 T cell tolerance: Partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis
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DOI：
10.1016/s1074-7613(00)80528-2
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发表时间：
1997-08-01
期刊：
影响因子：
32.4
通讯作者：
Goodnow, CC
中科院分区：
文献类型：
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作者：
Akkaraju, S;Ho, WY;Goodnow, CC
将对鸡蛋溶菌酶（HEL）具有特异性的T细胞受体（TCR）转基因小鼠与在甲状腺上皮、胰岛β细胞上或全身表达HEL的小鼠杂交。根据HEL表达的模式，双阳性胸腺细胞的缺失范围从最小到完全，外周CD 4细胞表现出TCR表达、体外反应性和体内辅助能力的分级降低。在TCR/甲状腺-HEL和TCR/胰岛-HEL小鼠中，CD 4细胞耐受性最低，这两种小鼠发展为广泛的淋巴细胞性甲状腺炎或胰岛炎，但不能消除表达HEL的内分泌细胞。因此，自身反应性CD 4克隆在一系列情况下逃离胸腺，当自身抗原集中在甲状腺或胰腺中时，保留足够的功能以启动亚临床自身免疫炎症，并且可以调节亚临床炎症向破坏性自身免疫疾病的进展。
T cell receptor (TCR) transgenic mice specific for hen egg lysozyme (HEL) were crossed with mice expressing HEL on the thyroid epithelium, on pancreatic islet beta cells, or systemically. Depending on the pattern of HEL expression, deletion of double-positive thymocytes ranged from minimal to complete, and peripheral CD4 cells exhibited graded reduction in TCR expression, in vitro responsiveness, and in vivo helper ability. CD4 cells were least tolerant in TCR/thyroid-HEL and TCR/islet-HEL mice, which developed an extensive lymphocytic thyroiditis or insulitis that nevertheless did not eliminate HEL-expressing endocrine cells. Autoreactive CD4 clones thus escape the thymus under a range of circumstances, retain sufficient function to initiate subclinical autoimmune inflammation when self-antigens are concentrated in the thyroid or pancreas, and may regulate progression of subclinical inflammation to destructive autoimmune disease.