Differences between two strains of myelin basic protein (MBP) TCR transgenic mice: implications for tolerance induction

J Autoimmun. 2002 Feb;18(1):27-37. doi: 10.1006/jaut.2001.0567.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ T cells which preferentially use the Vbeta8.2 TCR in response to myelin basic protein (MBP). Two strains of Tg mice (Valpha2.3/Vbeta8.2 and Valpha4/Vbeta8.2) have T cell receptors that recognize the NAc1-11 immunodominant epitope of MBP. We previously reported that oral administration of MBP protects both Valpha2.3/Vbeta8.2 and Valpha4/Vbeta8.2 mice from EAE; however, tolerance induction differs between strains and is dependent on the timing of oral antigen. Here we analyze the peripheral and gut-associated lymphoid tissue (GALT) environments of the two strains of Tg mice. Tg cells in the Peyer's patch (PP) but not the spleen of Valpha2.3/Vbeta8.2 mice demonstrate increased CD69 and decreased CD45RB relative to Valpha4/Vbeta8.2 mice. High levels of Th1 and Th2 cytokines, proliferative activity and CC chemokines (MCP-1) are observed in the periphery and GALT of Valpha2.3/Vbeta8.2 Tg mice. In contrast, more non-Tg CD4+ cells are seen in the PP of Valpha4/Vbeta8.2 mice. These studies suggest that activated Tg T cells and fewer potential regulatory cells in the PP of Valpha2.3/Vbeta8.2 Tg mice may influence oral tolerance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Separation
  • Chemokine CCL2 / metabolism
  • Cytokines / biosynthesis
  • Immune Tolerance / genetics*
  • Immunodominant Epitopes / administration & dosage
  • Immunodominant Epitopes / immunology
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin Basic Protein / administration & dosage
  • Myelin Basic Protein / immunology*
  • Peptide Fragments / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Species Specificity
  • Spleen / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Chemokine CCL2
  • Cytokines
  • Immunodominant Epitopes
  • Myelin Basic Protein
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • T-cell receptor Vbeta 8.2