The T-cell pool is anergized in patients with multiple sclerosis in remission

Immunology. 2009 Jan;126(1):92-101. doi: 10.1111/j.1365-2567.2008.02881.x. Epub 2008 Jun 24.


Relapsing-remitting multiple sclerosis (RRMS) is a complex autoimmune disease of the central nervous system with oscillating phases of relapse and remission. RRMS has been considered to be driven by T helper type 1 (Th1) lymphocytes but new data indicate the involvement of Th17 responses. In the present study, blood samples from patients (n=48) and healthy individuals (n=44) were evaluated for their immunological status. T cells from patients with RRMS expressed high levels of the activation marker CD28 (P<0.05) and secreted both interferon-gamma (CD8: P<0.05) and interleukin-17 upon polyclonal mitogen or myelin oligodendrocyte glycoprotein antigen stimulation. However, T cells from patients with RRMS in remission, in contrast to relapse, had poor proliferative capacity (P<0.05) suggesting that they are controlled and kept in anergy. This anergy could be broken with CD28 stimulation that restored the T-cell replication. Furthermore, the patients with RRMS had normal levels of CD4(+) Foxp3(+) T regulatory cells but the frequency of Foxp3(+) cells lacking CD127 (interleukin-7 receptor) was lower in patients with MS (mean 12%) compared to healthy controls (mean 29%). Still, regulatory cells (CD25(+) sorted cells) from patients with RRMS displayed no difference in suppressive capacity. In conclusion, patients in relapse/remission demonstrate in vitro T-cell responses that are both Th1 and Th17 that, while in remission, appear to be controlled by tolerogenic mechanisms yet to be investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Clonal Anergy / immunology*
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-17 / biosynthesis
  • Interleukin-7 Receptor alpha Subunit / analysis
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology


  • Interleukin-17
  • Interleukin-7 Receptor alpha Subunit
  • MOG protein, human
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Interferon-gamma