Estrogen treatment induces a novel population of regulatory cells, which suppresses experimental autoimmune encephalomyelitis

Agata Matejuk, Antony C. Bakke, Corwyn Hopke, Jami Dwyer, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Multiple sclerosis (MS) is a debilitating neurological disease characterized by a progressive loss of motor and sensory function, eventually leading to paralysis and death. The primary cause of neurological impairment is demyelination of the central nervous system (CNS) caused by an inflammatory autoimmune response. Previous studies have shown that the severity of MS is reduced during pregnancy, suggesting that the increased level of sex hormones may reduce the autoimmune response. Recently, we have shown that estrogen treatment confers protection from experimental autoimmune encephalomyelitis (EAE), which is an animal model for MS. However, the cellular basis of estrogen's action remains unknown. In the current study, we demonstrate that estrogen treatment led to the induction of a novel subpopulation of regulatory cells in spleen and CNS, which also occurs naturally in pregnant mice. These previously uncharacterized cells display a low level expression of CD45 (CD45dim) and no detectable expression of many cell surface markers related to TCR signaling, including CD3 and TCR. However, these cells retained expression of VLA-4, an extracellular protein involved in cellular migration. Several lines of evidence suggest that these novel cells, defined as CD45 dimVLA-4+ cells, may play a role in the protective effects of estrogen in EAE. Injection of purified CD45dimVLA-4+ cells conferred protection from spontaneous EAE (Sp-EAE). In contrast, injection of CD45highVLA-4+ cells exacerbated the disease course. CD45dimVLA-4+ cells also suppressed antigen-specific proliferation of primed lymphocytes in coculture. A better understanding of how CD45dimVLA-4+ cells suppress the harmful immune response of EAE may help in explaining the induction of immune tolerance during pregnancy and lead to novel therapeutic approaches to combat MS and other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalJournal of Neuroscience Research
Volume77
Issue number1
DOIs
StatePublished - Jul 1 2004

Keywords

  • CD45
  • EAE
  • Estrogen
  • Suppression

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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