Evidence against chronic antigen-specific T lymphocyte activation in myasthenia gravis

A. J. Infante, P. D. Infante, C. E. Jackson, R. J. Barohn, J. Tami, E. Iturriaga, S. Talib, E. Kraig, K. Z. Clarkin, K. A. Krolick

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Myasthenia gravis (MG) is an antigen-specific autoimmune disease caused by antibodies against acetylcholine receptors (AChR) at the post-synaptic membrane of the neuromuscular junction. Clinical and immunological data imply the involvement of AChR-specific T lymphocytes as helper cells for autoantibody production. Direct data to support this hypothesis, however, remain sparse. In the present study, a large population of MG patients was studied for evidence of peripheral blood T cell activation by several assays. Assays based on non-specific measurements of T cell activation as well as assays of antigenspecific clonal expansion were utilized. Levels of soluble IL-2 receptor in serum were modestly elevated in some patients, suggesting T cell activation. However, peripheral blood cells did not show evidence of IL- 2 receptor expression or enhanced reactivity to IL-2 in culture. Clonable T cells selected for hypoxanthine phosphoribosyl transferase (hprt) mutation, another non-antigen-specific marker for T cell activation, were not seen with increased frequency except in patients treated with purine analogs. Antigen- specific T cell activation was measured by proliferation assays using heterologous and autologous sources of AChR. Antigen-restimulated peripheral blood cell cultures were cloned by limiting dilution. The vast majority of patients failed to show convincing evidence of AChR specific T cell activation or clonal expansion; only 2 of 44 patients demonstrated clonable autologous AChR-specific T cells. An alternative hypothesis of T cell involvement in MG is proposed in which T cell activation is discontinuous and predominately directed at antigens other than AChR.

Original languageEnglish (US)
Pages (from-to)492-499
Number of pages8
JournalJournal of Neuroscience Research
Volume45
Issue number4
DOIs
StatePublished - 1996

Keywords

  • T cell activation
  • acetylcholine receptor
  • hprt mutant selection
  • soluble IL-2 receptor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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