Immune tolerance induced by intravenous transfer of immature dendritic cells via up-regulating numbers of suppressive IL-10(+) IFN-γ(+)-producing CD4(+) T cells

Immunol Res. 2013 May;56(1):1-8. doi: 10.1007/s12026-012-8382-7.

Abstract

Dendritic cells (DCs) regulate immunity and immune tolerance in vivo. However, the mechanisms of DC-mediated tolerance have not been fully elucidated. Here, we demonstrate that intravenous (i.v.) transfer of bone marrow-derived DCs pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide blocks the development of experimental autoimmune encephalomyelitis in C57BL/6J mice. i.v. transfer of MOG-pulsed DCs leads to the down-regulation of the production of IL-17A and IFN-γ and up-regulation of IL-10 secretion. The development of regulatory T cells (Tregs) is facilitated via up-regulation of FoxP3 expression and production of IL-10. The number of suppressive CD4(+)IL-10(+)IFN-γ(+) T cells is also improved. The expression of OX40, CD154, and CD28 is down-regulated, but the expression of CD152, CD80, PD-1, ICOS, and BTLA is up-regulated on CD4(+) T cells after i.v. transfer of immature DCs. The expression of CCR4, CCR5, and CCR7 on CD4(+) T cells is also improved. Our results suggest that immature DCs may induce tolerance via facilitating the development of CD4(+)FoxP3(+) Tregs and suppressive CD4(+)IL-10(+)IFN-γ(+) T cells in vivo.

Publication types

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

MeSH terms

  • Administration, Intravenous
  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation / immunology
  • Humans
  • Immune Tolerance
  • Immunosuppression Therapy
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / therapy*
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Chemokine
  • Interleukin-10
  • Interferon-gamma