Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis

J Neuroimmunol. 2013 Sep 15;262(1-2):72-8. doi: 10.1016/j.jneuroim.2013.07.001. Epub 2013 Jul 24.

Abstract

Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1β, TNF, IFN-γ, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3+ T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NFκB signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis.

Keywords: Apotransferrin; Experimental autoimmune encephalomyelitis; IL-2; T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoproteins / administration & dosage
  • Apoproteins / physiology*
  • Cells, Cultured
  • Down-Regulation / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Immunosuppressive Agents / administration & dosage
  • Interleukin-2 / antagonists & inhibitors*
  • Interleukin-2 / biosynthesis*
  • MAP Kinase Signaling System / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred NOD
  • NF-kappa B / antagonists & inhibitors
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transferrin / administration & dosage
  • Transferrin / physiology*

Substances

  • Apoproteins
  • Immunosuppressive Agents
  • Interleukin-2
  • NF-kappa B
  • Transferrin
  • apotransferrin