Direct ex vivo analysis of activated, Fas-sensitive autoreactive T cells in human autoimmune disease

J Exp Med. 1997 May 5;185(9):1585-94. doi: 10.1084/jem.185.9.1585.

Abstract

The frequency of clonally expanded and persistent T cells recognizing the immunodominant autoantigenic peptide of myelin basic protein (MBP)p85-99 was directly measured ex vivo in subjects with typical relapsing remitting multiple sclerosis (MS). T cells expressing mRNA transcripts encoding T cell receptor (TCR)-alpha and -beta chains found in T cell clones previously isolated from these subjects recognizing the MBPp85-99 epitope were examined. In contrast to frequencies of 1 in 10(5)-10(6) as measured by limiting dilution analysis, estimates of the T cell frequencies expressing MBPp85-99-associated TCR chain transcripts were as high as 1 in 300. These high frequencies were confirmed by performing PCR on single T cells isolated by flow cytometry. MBPp85-99 TCR transcripts were present in IL-2 receptor alpha-positive T cells which were induced to undergo Fas-mediated cell death upon antigen stimulation. These data demonstrate that at least a subpopulation of patients with MS can have a very high frequency of activated autoreactive T cells.

Publication types

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

MeSH terms

  • Autoantigens / immunology
  • Autoimmune Diseases / immunology*
  • Cell Death
  • Clone Cells
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Humans
  • Multiple Sclerosis / immunology*
  • Myelin Basic Protein / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocytes / immunology*
  • fas Receptor / physiology*

Substances

  • Autoantigens
  • Myelin Basic Protein
  • Receptors, Antigen, T-Cell, alpha-beta
  • fas Receptor