Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis

Ann Neurol. 2010 Oct;68(4):540-5. doi: 10.1002/ana.22065.

Abstract

Human mesenchymal stem cells (hMSCs) are being considered for clinical trials of multiple sclerosis (MS). We examined the effects of adult bone marrow-derived hMSCs on responses of primary human Th1, Th17, and Th1/17 double-expressing T-cell subsets, all implicated in MS. As expected, soluble products from hMSCs inhibited Th1 responses; however, Th17 responses were increased. Secretion of interleukin (IL)-10, considered anti-inflammatory, was decreased. Pretreating hMSCs with the proinflammatory cytokine IL-1β accentuated these effects, and caused decreases in the Th1/17 subset. These findings underscore the importance of further preclinical work and immune-monitoring to define hMSC effects on disease-relevant immune responses under variable conditions.

Publication types

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

MeSH terms

  • Antigens, CD / metabolism
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Cytokines / immunology
  • Cytokines / pharmacology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Flow Cytometry / methods
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / immunology*
  • T-Lymphocytes, Helper-Inducer / classification
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • Th1 Cells / cytology*
  • Th1 Cells / immunology

Substances

  • Antigens, CD
  • Culture Media, Conditioned
  • Cytokines