Mouse Schwann cells activate MHC class I and II restricted T-cell responses, but require external peptide processing for MHC class II presentation

Neurobiol Dis. 2010 Feb;37(2):483-90. doi: 10.1016/j.nbd.2009.11.006. Epub 2009 Nov 13.

Abstract

Schwann cells are the myelinating glia cells of the peripheral nervous system (PNS). In inflammatory neuropathies like the Guillain-Barré syndrome (GBS) Schwann cells become target of an autoimmune response, but may also modulate local inflammation. Here, we tested the functional relevance of Schwann cell derived MHC expression in an in vitro coculture system. Mouse Schwann cells activated proliferation of ovalbumin specific CD8+ T cells when ovalbumin protein or MHC class I restricted ovalbumin peptide (Ova(257-264) SIINFEKL) was added and after transfection with an ovalbumin coding vector. Schwann cells activated proliferation of ovalbumin specific CD4+ T cells in the presence of MHC class II restricted ovalbumin peptide (Ova(323-339) ISQAVHAAHAEINEAGR). CD4+ T-cell proliferation was not activated by ovalbumin protein or transfection with an ovalbumin coding vector. This indicates that Schwann cells express functionally active MHC class I and II molecules. In this study, however, Schwann cells lacked the ability to process exogenous antigen or cross-present endogenous antigen into the MHC class II presentation pathway. Thus, antigen presentation may be a pathological function of Schwann cells exacerbating nerve damage in inflammatory neuropathies.

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Genetic Vectors / pharmacology
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Major Histocompatibility Complex / physiology*
  • Mice
  • Mice, Transgenic
  • Neuritis / immunology*
  • Neuritis / metabolism
  • Neuritis / physiopathology
  • Open Reading Frames / genetics
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology
  • Peptides / metabolism
  • Peripheral Nerves / immunology
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / physiopathology
  • Peripheral Nervous System Diseases / immunology*
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / physiopathology
  • Schwann Cells / immunology*
  • Schwann Cells / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transfection

Substances

  • Biomarkers
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • OVA-8
  • Peptide Fragments
  • Peptides
  • Ovalbumin