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Cell Physiol Biochem. 2013;32(4):827-37. doi: 10.1159/000354485. Epub 2013 Sep 20.

CD8(+) T cell-mediated cytotoxicity toward Schwann cells promotes diabetic peripheral neuropathy.

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  • 1Department of Endocrinology, Shanghai Changzheng Hospital, Shanghai, PR China.

Abstract

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.

© 2013 S. Karger AG, Basel

PMID:
24080983
[PubMed - indexed for MEDLINE]
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