Induction of regulatory T-cells from memory T-cells is perturbed during acute exacerbation of multiple sclerosis

Clin Immunol. 2016 May:166-167:12-8. doi: 10.1016/j.clim.2016.05.001. Epub 2016 May 3.

Abstract

Regulatory T-cells (Tregs) are vital for maintaining immunological self-tolerance, and the transcription factor FOXP3 is considered critical for their development and function. Peripheral Treg induction may significantly contribute to the total Treg pool in healthy adults, and this pathway may be enhanced in thymic-deficient conditions like multiple sclerosis (MS). Here, we evaluated iTreg formation from memory versus naïve CD4(+)CD25(-) T-cell precursors. We report the novel finding that memory T-cells readily expressed CD25 and FOXP3, and demonstrated significantly greater suppressive function. Additionally, the CD25(-)FOXP3(-) fraction of stimulated memory T-cells also displayed robust suppression not observed in naïve counterparts or ex vivo resting (CD25(-)) T-cells. This regulatory population was present in both healthy subjects and clinically-quiescent MS patients, but was specifically deficient during disease exacerbation. These studies indicate that iTreg development and function are precursor dependent. Furthermore, MS quiescence appears to correlate with restoration of suppressive function in memory-derived CD4(+)CD25(-)FOXP3(-) iTregs.

Keywords: FOXP3; Immune regulation; Memory; Multiple sclerosis; Naïve; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Antibodies / pharmacology
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology*
  • Case-Control Studies
  • Cell Differentiation
  • Forkhead Transcription Factors / deficiency
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Gene Expression
  • Humans
  • Immune Tolerance
  • Immunologic Memory*
  • Interleukin-2 Receptor alpha Subunit / deficiency
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Lymphocyte Activation / drug effects
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • Primary Cell Culture
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Antibodies
  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit