Lehuen A, Lantz O, Beaudoin L, Laloux V, Carnaud C, Bendelac A, Bach J F, Monteiro R C
INSERM U 25, Hôpital Necker, 75743 Paris, France.
J Exp Med. 1998 Nov 16;188(10):1831-9. doi: 10.1084/jem.188.10.1831.
Progression to destructive insulitis in nonobese diabetic (NOD) mice is linked to the failure of regulatory cells, possibly involving T helper type 2 (Th2) cells. Natural killer (NK) T cells might be involved in diabetes, given their deficiency in NOD mice and the prevention of diabetes by adoptive transfer of alpha/beta double-negative thymocytes. Here, we evaluated the role of NK T cells in diabetes by using transgenic NOD mice expressing the T cell antigen receptor (TCR) alpha chain Valpha14-Jalpha281 characteristic of NK T cells. Precise identification of NK1.1(+) T cells was based on out-cross with congenic NK1.1 NOD mice. All six transgenic lines showed, to various degrees, elevated numbers of NK1.1(+) T cells, enhanced production of interleukin (IL)-4, and increased levels of serum immunoglobulin E. Only the transgenic lines with the largest numbers of NK T cells and the most vigorous burst of IL-4 production were protected from diabetes. Transfer and cotransfer experiments with transgenic splenocytes demonstrated that Valpha14-Jalpha281 transgenic NOD mice, although protected from overt diabetes, developed a diabetogenic T cell repertoire, and that NK T cells actively inhibited the pathogenic action of T cells. These results indicate that the number of NK T cells strongly influences the development of diabetes.
非肥胖型糖尿病（NOD）小鼠发展为破坏性胰岛炎与调节性细胞功能衰竭有关，可能涉及2型辅助性T细胞（Th2）。鉴于NOD小鼠中自然杀伤（NK）T细胞缺乏，以及通过α/β双阴性胸腺细胞的过继转移可预防糖尿病，NK T细胞可能参与糖尿病的发生。在此，我们通过使用表达NK T细胞特征性T细胞抗原受体（TCR）α链Valpha14-Jalpha281的转基因NOD小鼠，评估了NK T细胞在糖尿病中的作用。基于与同基因NK1.1 NOD小鼠的杂交，对NK1.1(+) T细胞进行精确鉴定。所有六个转基因品系均不同程度地显示出NK1.1(+) T细胞数量增加、白细胞介素（IL）-4产生增强以及血清免疫球蛋白E水平升高。只有NK T细胞数量最多且IL-4产生最活跃的转基因品系对糖尿病具有抵抗力。用转基因脾细胞进行的转移和共转移实验表明，Valpha14-Jalpha281转基因NOD小鼠虽然对显性糖尿病具有抵抗力，但仍产生致糖尿病性T细胞库，且NK T细胞可积极抑制T细胞的致病作用。这些结果表明，NK T细胞的数量强烈影响糖尿病的发展。
