Rymarchyk Stacia L, Lowenstein Hayden, Mayette Jana, Foster Samantha R, Damby David E, Howe Isaac W, Aktan Idil, Meyer Russell E, Poynter Matthew E, Boyson Jonathan E
Department of Surgery, Univeristy of Vermont College of Medicine, Burlington, VT 05405, USA.
Immunology. 2008 Nov;125(3):331-43. doi: 10.1111/j.1365-2567.2008.02846.x. Epub 2008 Apr 26.
Natural killer T (NKT) cells comprise a novel T-lymphocyte subset that can influence a wide variety of immune responses through their ability to secrete large amounts of a variety of cytokines. Although variation in NKT-cell number and function has been extensively studied in autoimmune disease-prone mice, in which it has been linked to disease susceptibility, relatively little is known of the natural variation of NKT-cell number and function among normal inbred mouse strains. Here, we demonstrate strain-dependent variation in the susceptibility of C57BL/6J and BALB/cJ mice to NKT-mediated airway hyperreactivity, which correlated with significant increases in serum interleukin-4 (IL-4) and IL-13 elicited by the synthetic glycosphingolipid alpha-galactosylceramide. Examination of NKT-cell function revealed a significantly greater frequency of cytokine-producing NKT cells in C57BL/6J versus BALB/cJ mice as well as significant differences in the kinetics of NKT-cell cytokine production. Extension of this analysis to a panel of inbred mouse strains indicated that variability in NKT-cell cytokine production was widespread. Similarly, an examination of NKT-cell frequency revealed a significantly greater number of liver NKT cells in the C57BL/6J mice versus BALB/cJ mouse livers. Again, examination of a panel of inbred mouse strains revealed that liver NKT-cell numbers were quite variable, spanning over a 100-fold range. Taken together, these results demonstrate the presence of widespread natural variation in NKT-cell number and function among common inbred mouse strains, which may have implications for the examination of the influence of NKT cells in immune responses and disease pathogenesis among different genetic backgrounds.
自然杀伤T（NKT）细胞是一种新型的T淋巴细胞亚群，它能够通过分泌大量多种细胞因子来影响多种免疫反应。尽管在易患自身免疫性疾病的小鼠中，NKT细胞数量和功能的变化已得到广泛研究，且其与疾病易感性相关，但对于正常近交系小鼠品系中NKT细胞数量和功能的自然变异却知之甚少。在此，我们证明了C57BL/6J和BALB/cJ小鼠对NKT介导的气道高反应性的易感性存在品系依赖性差异，这与合成糖鞘脂α-半乳糖神经酰胺引发的血清白细胞介素-4（IL-4）和IL-13显著增加相关。对NKT细胞功能的检测显示，与BALB/cJ小鼠相比，C57BL/6J小鼠中产生细胞因子的NKT细胞频率显著更高，并且NKT细胞产生细胞因子的动力学也存在显著差异。将该分析扩展至一组近交系小鼠品系表明，NKT细胞产生细胞因子的变异性广泛存在。同样，对NKT细胞频率的检测显示，C57BL/6J小鼠肝脏中的NKT细胞数量明显多于BALB/cJ小鼠肝脏。再次，对一组近交系小鼠品系的检测表明，肝脏NKT细胞数量变化很大，跨度超过100倍。综上所述，这些结果表明在常见近交系小鼠品系中，NKT细胞数量和功能存在广泛的自然变异，这可能对研究不同遗传背景下NKT细胞在免疫反应和疾病发病机制中的影响具有重要意义。
