Changes of Treg-associated molecules on CD4+CD25 +Treg cells in myasthenia gravis and effects of immunosuppressants

J Clin Immunol. 2012 Oct;32(5):975-83. doi: 10.1007/s10875-012-9685-0. Epub 2012 Mar 31.

Abstract

Objective: Myasthenia gravis (MG) is a CD4(+) T cell-dependent autoimmune disease, and close attention has been paid to the role of CD4(+)CD25(+)Treg cells (Tregs). Previous results regarding Tregs in MG patients have been conflicting. The discrepancy was partly ascribed to selecting different Treg-associated molecules in defining Tregs. Therefore, we considered it necessary to find a reliable index for assessing the immunologic state in MG patients and explore the effect of IS on them.

Methods: We adopted flow cytometric techniques to measure the numbers and frequencies of Tregs in peripheral blood taken from 57 patients and 91 age-matched healthy donors, and we also analyzed FOXP3 mean fluorescence intensity on Tregs.

Results: The number and frequency of Tregs in peripheral blood of MG patients significantly decreased, together with down-regulation of FOXP3 expression. There was dynamic change of Treg cell level and the inverse relationship with clinical symptom, suggesting that the immunologic disorder in MG patients was related to peripheral Tregs population. Meanwhile, CD4(+)CD25(+)FOXP3(+)Helios(+)T cells might be activated Tregs, rather than nTregs. Moreover, the number and frequency of CD4(+)CD25(+)FOXP3(+)Helios(+)T cells significantly decreased in MG patients, indicating that the reduction of the activated Tregs population might be a critical contributor to the pathogenesis of MG.

Conclusions: The significant reduction of the peripheral Tregs population in MG patients might be responsible for the immunologic disorders in MG patients. IS such as GC took its effect possible by increasing the population size, and the underlying mechanism should be further investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Antigens / immunology
  • CD4 Lymphocyte Count
  • Female
  • Forkhead Transcription Factors / immunology
  • Humans
  • Ikaros Transcription Factor / immunology
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Myasthenia Gravis / immunology*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Young Adult

Substances

  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IKZF2 protein, human
  • IL2RA protein, human
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Ikaros Transcription Factor