St Vincent's Institute, Fitzroy, Melbourne, Australia.
Immunol Cell Biol. 2012 Feb;90(2):243-7. doi: 10.1038/icb.2011.16. Epub 2011 Mar 8.
CD8(+) T cells kill pancreatic β-cells in a cell-cell contact-dependent mechanism in the non-obese diabetic mouse. CD4(+) T lymphocytes are also able to kill pancreatic β-cells, but they do not directly contact β-cells and may use another cell type as the actual cytotoxic cell. Natural killer (NK) cells could have this role but it is uncertain whether they are cytotoxic towards β-cells. Therefore, the requirement for NK cells in β-cell destruction in the CD4-dependent T-cell antigen receptor transgenic NOD4.1 mice was examined. NK cells failed to kill β-cells in vitro, even in the absence of major histocompatibility complex class I. We observed only 9.7±1.1% of islet infiltrating NK cells from NOD4.1 mice expressing the degranulation marker CD107a. Diabetogenic CD4(+) T cells transferred disease to NODscid.IL2Rγ(-/-) mice lacking NK cells, indicating that NK cells do not contribute to β-cell death in vitro or in vivo. However, depletion of NK cells reduced diabetes incidence in NOD4.1 mice, suggesting that NK cells may help to maintain the right environment for cytotoxicity of effector cells.
CD8(+) T 细胞通过非肥胖型糖尿病小鼠中的细胞间接触依赖性机制杀伤胰岛β细胞。CD4(+) T 淋巴细胞也能够杀伤胰岛β细胞，但它们并不直接接触β细胞，而是可能利用另一种细胞作为实际的细胞毒性细胞。自然杀伤 (NK) 细胞可能具有这种作用，但尚不确定它们是否对β细胞具有细胞毒性。因此，在 CD4 依赖性 T 细胞抗原受体转基因 NOD4.1 小鼠中，研究了 NK 细胞在β细胞破坏中的作用。NK 细胞即使在缺乏主要组织相容性复合体 I 类的情况下，也未能在体外杀伤β细胞。我们仅观察到 9.7±1.1%来自表达脱颗粒标志物 CD107a 的 NOD4.1 小鼠的胰岛浸润 NK 细胞。具有致糖尿病作用的 CD4(+) T 细胞将疾病转移到缺乏 NK 细胞的 NODscid.IL2Rγ(-/-)小鼠中，表明 NK 细胞在体外或体内均不会导致β细胞死亡。然而，NK 细胞的耗竭降低了 NOD4.1 小鼠的糖尿病发病率，这表明 NK 细胞可能有助于维持效应细胞细胞毒性的适当环境。
