T-cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls

J Neurosci Res. 2001 Feb 1;63(3):290-302. doi: 10.1002/1097-4547(20010201)63:3<290::AID-JNR1023>3.0.CO;2-4.

Abstract

Myelin proteins, including myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) are candidate autoantigens in MS. It is not clear whether MS patients show a predominant reactivity to one or several myelin antigens. We evaluated the IFN-gamma production induced by MBP and MOG and selected MBP-, MOG- and PLP-peptides in MS patients and healthy controls using the IFN-gamma ELISPOT assay. Most MS patients and healthy controls showed a heterogeneous anti-myelin T-cell reactivity. Interestingly in MS patients a positive correlation was found between the anti-MOG and anti-MBP T-cell responses. No myelin peptide was preferentially recognized among the peptides tested (MBP 84-102, 143-168, MOG 1-22, 34-56, 64-86, 74-96, PLP 41-58, 184-199, 190-209). In addition the frequency of IL2R+ MBP reactive T-cells was significantly increased in blood of MS patients as compared with healthy subjects, indicating that MBP reactive T-cells exist in an in vivo activated state in MS patients. Most of the anti-MBP T-cells were of the Th1-type because reactivity was observed in IFN-gamma but not in IL-4 ELISPOT-assays. Using Th1 (IL-12) and Th2 (IL-4) promoting conditions we observed that the cytokine secretion pattern of anti-MBP T-cells still is susceptible to alteration. Our data further indicate that precursor frequency analysis of myelin reactive T-cells by proliferation-based assays may underestimate the true frequency of myelin specific T-cells significantly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens / blood
  • Antigens / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-12 / pharmacology
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / physiopathology
  • Myelin Basic Protein / blood
  • Myelin Basic Protein / immunology
  • Myelin Proteins / blood
  • Myelin Proteins / immunology*
  • Myelin Proteolipid Protein / blood
  • Myelin Proteolipid Protein / immunology
  • Myelin-Associated Glycoprotein / blood
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antigens
  • Interleukin-2
  • MOG protein, human
  • Myelin Basic Protein
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma