Mora C, Wong F S, Chang C H, Flavell R A
Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520, USA.
J Immunol. 1999 Apr 15;162(8):4576-88.
The NOD (nonobese diabetic) mouse is a good animal model for human IDDM. MHC class II-restricted CD4 T cells are necessary for the onset of diabetes in NOD mice. Here, we demonstrate that NOD mice lacking the CIITA (class II transactivator) molecule, and hence deficient in MHC class II expression and peripheral CD4 T cells, show significant pancreatic infiltration but do not develop diabetes. CD4 T cell deficiency, then, does not prevent initial pancreatic infiltration, but does stop progression to insulitis. Adoptive transfer studies show that the paucity of CD4 T cells in NOD-CIITA knockout mice is responsible for the absence of diabetes, since the CD8 T cell and B cell compartments are functional. An autoaggressive CD8+ T cell clone can, however, transfer diabetes in CIITA knockout recipient mice without CD4 T cell help, albeit with some delay compared with that in CIITA-sufficient recipients. This highlights the fact that a high number of in vitro activated autoaggressive CD8 T cells can over-ride the requirement for CD4 T cell help for the onset of diabetes.
非肥胖型糖尿病（NOD）小鼠是人类胰岛素依赖型糖尿病（IDDM）的良好动物模型。MHC II类分子限制性CD4 T细胞对于NOD小鼠糖尿病的发生是必需的。在此，我们证明，缺乏II类反式激活因子（CIITA）分子，因而MHC II类分子表达缺陷且外周CD4 T细胞缺乏的NOD小鼠，显示出显著的胰腺浸润，但并未发生糖尿病。因此，CD4 T细胞缺乏并不妨碍最初的胰腺浸润，但会阻止其发展为胰岛炎。过继转移研究表明，NOD-CIITA基因敲除小鼠中CD4 T细胞的缺乏是其未发生糖尿病的原因，因为CD8 T细胞和B细胞区室功能正常。然而，一个自身攻击性CD8+ T细胞克隆能够在没有CD4 T细胞帮助的情况下，使CIITA基因敲除的受体小鼠发生糖尿病，尽管与CIITA充足的受体小鼠相比会有一些延迟。这突出了一个事实，即大量体外激活的自身攻击性CD8 T细胞能够克服糖尿病发生对CD4 T细胞帮助的需求。
