CD8+ T Cell-Mediated Cytotoxicity toward Schwann Cells Promotes Diabetic Peripheral Neuropathy

• Main Authors: Wei Tang, Qian Lv, Xiang-fang Chen, Jun-jie Zou, Zhi-min Liu, Yong-quan Shi
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2013-09-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Schwann cells; Cytotoxicity; Diabetic peripheral neuropathy; CXCR3; CD8+ T cells
• Online Access: http://www.karger.com/Article/FullText/354485
• ISSN: 1015-8987; 1421-9778

Background: Damage to Schwann cells has been reported in the development of diabetic peripheral neuropathy (DPN), but how Schwann cells are damaged has not been elucidated. Methods: The highly expressed proteins in the PBMC of DPN patients were identified through MALDI-TOF/TOF and SELDI protein chip technology. The expression levels of CXCR3 were detected by qPCR and flow cytometric analysis. Transwell migration assay was to investigate the migration of CD8+ T cells. Western-blot analysis was to detect the levels of p38 MAP kinases pathway related proteins and TNF-α, FasL, and PDL1. Results: Two highly expressed proteins, CXCR3 and p38, were identified. Under high glucose conditions, CXCR3 was elevated in CD8+ T cells via the activation of p38 MAP kinases. Moreover, CXCL9, CXCL10, and CXCL11 expression were induced in Schwann cells, leading to the recruitment and infiltration of CD8+ T cells into DPN tissues. Further study demonstrated that Schwann cells promoted activation of CD8+ T cells and induced expression of TNF-α, FasL, and PDL1 on CD8+ T cells, in return, CD8+ T cells induced obvious apoptosis of Schwann cells. Conclusion: Our study indicates that CD8+ T cells mediate cytotoxicity toward Schwann cells and play an important role in the development of DPN.