酚糖脂 1 和脂阿拉伯甘露聚糖优先调节 TCR 和 CD28 触发的近端生化事件，导致分枝杆菌病中的 T 细胞无反应性。

Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases.

机构信息

Immunology Laboratory, National JALMA Institute for Leprosy and Other Mycobacterial Diseases-ICMR, Dr. M. Miyazaki Marg, Tajganj, Agra 282001, India.

出版信息

Lipids Health Dis. 2012 Sep 17;11:119. doi: 10.1186/1476-511X-11-119.

BACKGROUND

Advanced stages of leprosy show T cell unresponsiveness and lipids of mycobacterial origin are speculated to modulate immune responses in these patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- mediated signalling.

RESULTS

We observed that lipid antigens significantly inhibit proximal early signalling events like Zap-70 phosphorylation and calcium mobilization. Interestingly, these antigens preferentially curtailed TCR-triggered early downstream signalling events like p38 phosphorylation whereas potentiated that of Erk1/2. Further, at later stages inhibition of NFAT binding, IL-2 message, CD25 expression and T-cell blastogenesis by PGL-1 and Man-LAM was noted.

CONCLUSION

Altogether, we report that Man-LAM and PGL-1 preferentially interfere with TCR/CD28-triggered upstream cell signalling events, leading to reduced IL-2 secretion and T-cell blastogenesis which potentially could lead to immunosupression and thus, disease exacerbation, as noted in disease spectrum.

背景

麻风病的晚期阶段表现出 T 细胞无反应性，推测分枝杆菌来源的脂质可以调节这些患者的免疫反应。本研究阐明了酚基甘油糖脂（PGL-1）和甘露糖封端的脂阿拉伯甘露聚糖（Man-LAM）在 TCR 和 TCR/CD28 介导的信号转导中的作用。

结果

我们观察到脂质抗原显著抑制 Zap-70 磷酸化和钙动员等早期近端信号事件。有趣的是，这些抗原优先抑制 TCR 触发的早期下游信号事件，如 p38 磷酸化，而增强 Erk1/2 的磷酸化。此外，还观察到 PGL-1 和 Man-LAM 在后期抑制 NFAT 结合、IL-2 消息、CD25 表达和 T 细胞增殖。