Distribution of Foxp3(+) T-regulatory cells in experimental autoimmune neuritis rats

Exp Neurol. 2009 Mar;216(1):75-82. doi: 10.1016/j.expneurol.2008.11.014. Epub 2008 Dec 3.

Abstract

T-regulatory cells expressing the forkhead box transcription factor 3 (Foxp3) play essential roles in immune homeostasis. Experimental autoimmune neuritis (EAN) is an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system. We investigated the distribution of Foxp3(+) cells in sciatic nerves, spleen and lymph nodes of EAN rats, and the influence of FTY720 on the localization of Foxp3(+) cells in EAN rats. In sciatic nerves of EAN rats, accumulation of Foxp3(+) cells was not seen during the pre-symptomatic phase (until Day 9) or during early or peak disease activity. In contrast, Foxp3(+) cell accumulation was regularly seen in the recovery from neurologic disease, suggesting a contribution of Foxp3(+) cells to the resolution of EAN. FTY720 was given at onset of EAN (Day 10) until Day 18. Following FTY720 administration, percentages of Foxp3(+) cells in EAN rats were increased in circulating blood, but reduced in lymph nodes compared to the PBS control. FTY720 treatment suppressed total numbers but increased percentages of Foxp3(+) cells in sciatic nerves of EAN rats. These data not only suggests a protective role of Foxp3(+) cells in EAN but also provides a potential way to alter localization of Foxp3(+) cells in vivo.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Fingolimod Hydrochloride
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / metabolism*
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunosuppressive Agents / pharmacology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / physiopathology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / metabolism
  • Lymphoid Tissue / physiopathology
  • Male
  • Neuritis, Autoimmune, Experimental / immunology
  • Neuritis, Autoimmune, Experimental / metabolism
  • Neuritis, Autoimmune, Experimental / physiopathology
  • Polyradiculoneuropathy / immunology*
  • Polyradiculoneuropathy / metabolism
  • Polyradiculoneuropathy / physiopathology
  • Propylene Glycols / pharmacology
  • Rats
  • Rats, Inbred Lew
  • Sciatic Nerve / immunology*
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / physiopathology
  • Sphingosine / analogs & derivatives
  • Sphingosine / pharmacology
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / physiopathology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, rat
  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine