Role of MOG-stimulated Th1 type "light up" (GFP+) CD4+ T cells for the development of experimental autoimmune encephalomyelitis (EAE)

J Autoimmun. 2001 Aug;17(1):17-25. doi: 10.1006/jaut.2001.0520.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis in humans. EAE can be passively transferred into naive syngeneic animals by administration of MOG-specific T cell clones. Lymphocytes isolated from green fluorescent protein (GFP)-transgenic (Tg) mice can light up by emitting green fluorescence, thus making it feasible to use such animals in a passive transfer model for EAE. When MOG-sensitized splenic lymphocytes from GFP-Tg mice were adoptively transferred to irradiated, syngeneic C57BL/6 and RAG-1(-/-)mice, typical symptoms of EAE developed. Analysis of the reconstituted mice with EAE revealed prominent infiltration of fluorescing (GFP+), CD4+ T cells into the central nervous system (CNS). Real-time confocal imaging revealed these cells in the spinal cords and brains of recipient mice. This infiltration was also confirmed by anti-GFP monoclonal antibodies. Furthermore, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation indicated that the infiltrating GFP+, CD4+ T cells exclusively produced T helper type 1 (Th1) cytokines, especially interferon-gamma (IFN-gamma). These results clearly show that MOG-specific CD4+ T cells preferentially invade into the CNS and mediate the development of EAE by producing Th1-biased cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / chemistry
  • Antigens, Surface / immunology
  • Brain / immunology
  • Brain / pathology
  • Cell Movement / immunology
  • Cytokines / biosynthesis
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Female
  • Green Fluorescent Proteins
  • Luminescent Proteins / biosynthesis*
  • Luminescent Proteins / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / chemistry
  • Myelin-Associated Glycoprotein / immunology*
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / immunology
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / pathology

Substances

  • Antigens, Surface
  • Cytokines
  • Luminescent Proteins
  • MOG protein, human
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Green Fluorescent Proteins