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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL11 / metabolism
  • Chemokine CXCL9 / metabolism
  • Diabetic Neuropathies / metabolism*
  • Flow Cytometry
  • Glucose / adverse effects
  • Humans
  • Peripheral Nervous System Diseases / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, CXCR3 / metabolism
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Receptors, CXCR3
  • p38 Mitogen-Activated Protein Kinases
  • Glucose