Transfer of severe experimental autoimmune encephalomyelitis by IL-12- and IL-18-potentiated T cells is estrogen sensitive

Atsushi Ito, Agata Matejuk, Corwyn Hopke, Heather Drought, Jami Dwyer, Alex Zamora, Sandhya Subramanian, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The aim of this study was to evaluate the roles of IL-18 and IL-12 in potentiating the encephalitogenic activity of T cell lines specific for myelin oligodendrocyte glycoprotein (MOG35-5). MOG-specific T cells stimulated with anti-CD3 and anti-CD28 in the presence of IL-12 or IL-18 alone transferred only mild experimental autoimmune encephalomyelitis (EAE) into a low percentage of recipients. However, T cells cocultured with both cytokines transferred aggressive clinical and histological EAE into all recipients. Coculture of T cells with IL-12 enhanced the secretion of IFN-γ but not TNF-α, whereas coculture with IL-18 enhanced the secretion of TNF-α, but not INF-γ. However, coculture with both IL-18 and IL-12 induced high levels of both TNF-α and IFN-γ. Additionally, IL-12 selectively enhanced mRNA expression of CCR5, whereas IL-18 selectively enhanced the expression of CCR4 and CCR7, and CCR4 and CCR5 were coexpressed on the surface of T cells cocultured with IL-12 and IL-18. Finally, estrogen treatment, previously found to inhibit both TNF-α and IFN-γ production, completely abrogated all signs of passive EAE. These data demonstrate that optimal potentiation of encephalitogenic activity can be achieved by conditioning MOG-specific T cells with the combination of IL-12 and IL-18, which, respectively, induce the secretion of IFN-γ/CCR5 and TNF-γ/CCR4/CCR7, and that estrogen treatment, which is known to inhibit both proinflammatory cytokines, can completely ablate this aggressive form of passive EAE.

Original languageEnglish (US)
Pages (from-to)4802-4809
Number of pages8
JournalJournal of Immunology
Volume170
Issue number9
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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