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

Autor: Wei Tang, Qian Lv, Xiang-fang Chen, Jun-jie Zou, Zhi-min Liu, Yong-quan Shi
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Cellular Physiology and Biochemistry, Vol 32, Iss 4, Pp 827-837 (2013)
Druh dokumentu: article
ISSN: 1015-8987
1421-9778
DOI: 10.1159/000354485
Popis: 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.
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