The effect of follicular cytotoxic T cells in the process of immune injury in non⁃obese diabetic mice
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摘要:
目的：探讨滤泡细胞毒性T细胞（follicular cytotoxic T cells，TFC）的特点及其在非肥胖糖尿病（non-obese diabetic，NOD）小鼠自身免疫性糖尿病病程中发挥的作用。方法：分离4、10、15、20、25周龄及高血糖（hyperglycemia，Hi）组NOD小鼠的脾脏、淋巴结及胸腺淋巴细胞并进行流式染色，通过流式检测观察并比较TFC和CXCR5-CD8+T细胞在不同免疫器官中的分布情况、在自身免疫性糖尿病自然病程中的细胞比例变化、脱颗粒标记物白细胞分化抗原（cluster of differentiation 107a，CD107a）、重组人杀伤细胞凝集素样受体 G亚族成员1（recombinant human killer cell lectin-like receptor subfamily G，member 1，KLRG1）、抑制性分子程序性死亡分子1（programmed cell death protein 1，PD-1）和T细胞免疫球蛋白黏蛋白结构分子3（T cell immunoglobulin mucin 3，TIM-3）的表达水平以及2种细胞释放干扰素γ（interferon γ，IFN-γ）、颗粒酶B（granzyme B，GzmB）的能力。结果：TFC在NOD鼠不同免疫器官间表达存在差异，在脾脏和淋巴结中表达量相当，而在胸腺几乎无表达。在NOD小鼠血糖升高前，随着周龄的增加TFC细胞比例呈现逐渐上升趋势，发病后比例下降。与CXCR5-CD8+T细胞相比，TFC细胞比例明显较低，但抑制性分子PD-1、TIM-3和脱颗粒标记物CD107a却呈显著性高表达。与此同时，TFC较CXCR5-CD8+T细胞具有更强地释放GzmB［TFC（3.56±2.1）%，CXCR5-CD8+T细胞（0.78±0.39）%，P < 0.05］和IFN-γ［TFC（43.65±12.25）%，CXCR5-CD8+T细胞（21.92±3.72）%，P < 0.05］的能力。结论：TFC存在并参与NOD小鼠自身免疫性糖尿病的自然病程，并通过细胞毒性作用促进NOD小鼠的免疫损伤。
Abstract:
Objective：This study aims to explore the characteristics of follicular cytotoxic T cells（TFC）and the role they played in the natural course of autoimmune diabetes in non-obese diabetic（NOD） mice. Methods：The spleen，lymph nodes and thymus lymphocytes of NOD mice in 4 weeks，10 weeks，15 weeks，20 weeks，25 weeks，and hyperglycemia（Hi） groups were separated and stained by flow cytometry antibodies. Through flow cytometry，we observed and compared the distribution of TFC and CXCR5-CD8+T cells in different immune organs，the changes of cell proportion in the natural course of autoimmune diabetes，the expression levels of degranulation markers cluster of differentiation 107a（CD107a） and recombinant human killer cell lectin-like receptor subfamily G，member 1（KLRG1），inhibitory molecules programmed cell death protein 1（PD-1） and T cell immunoglobulin mucin 3（TIM-3），and the ability of releasing interferon γ（IFN-γ）and granzyme B（GzmB）. Results：The results of this study illustrated that the expression and distribution of TFC was different in various immune organs of NOD mice. The expression levels in the spleen and lymph nodes were equivalent，but there was almost no expression in the thymus. Before the blood sugar of NOD mice increased，the proportion of TFC cells showed a gradual upward trend along with the increasing age，which decreased after the onset. Compared with CXCR5-CD8+T cells，the proportion of TFC was significantly lower，but the inhibitory molecules PD-1，TIM-3 and the degranulation marker CD107a expressed on TFC were significantly higher. At the same time，TFC has a stronger ability to release GzmB［TFC（3.56±2.1）%；CXCR5-CD8+T cell（0.78±0.39）%，P < 0.05］and IFN-γ［TFC（43.65±12.25）%；CXCR5-CD8+T cell（21.92±3.72）%，P < 0.05］than CXCR5-CD8+ T cells. Conclusion：TFC exists and participates in the natural course of autoimmune diabetes in NOD mice，and promotes immune damage in NOD mice through cytotoxic effect.
