Serreze D V
Jackson Laboratory, Bar Harbor, Maine 04609.
FASEB J. 1993 Aug;7(11):1092-6. doi: 10.1096/fasebj.7.11.8370480.
In most cases, insulin-dependent diabetes results from autoimmune elimination of pancreatic beta cells by T lymphocytes that are generated as a result of complex polygenic interactions between particular MHC haplotypes and non-MHC linked susceptibility modifiers. Immature T cells with potential autoreactivity are normally destroyed in the thymus when they are highly activated after ligation of the T cell receptor (TCR) with "self" peptides bound to MHC molecules on antigen presenting cells (APC) such as macrophages. Here the hypothesis is put forth that non-MHC linked diabetes susceptibility genes contribute to subtle defects in the maturation of macrophages, and in synergy with a diabetogenic MHC haplotype generate APC that are unable to trigger autoreactive T cells to an activation state high enough to induce their destruction.
在大多数情况下，胰岛素依赖型糖尿病是由T淋巴细胞对胰腺β细胞进行自身免疫清除所致，这些T淋巴细胞是特定MHC单倍型与非MHC连锁易感性修饰因子之间复杂多基因相互作用的结果。具有潜在自身反应性的未成熟T细胞，在与抗原呈递细胞（如巨噬细胞）上与MHC分子结合的“自身”肽段结合后，T细胞受体（TCR）高度活化，此时通常会在胸腺中被破坏。这里提出的假说是，非MHC连锁的糖尿病易感性基因导致巨噬细胞成熟存在细微缺陷，并与致糖尿病的MHC单倍型协同作用，产生无法将自身反应性T细胞触发到足以诱导其破坏的高活化状态的抗原呈递细胞。
