Critical involvement of OX40 ligand signals in the T cell priming events during experimental autoimmune encephalomyelitis

L. C. Ndhlovu, N. Ishii, K. Murata, T. Sato, K. Sugamura

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89 Citations (Scopus)

Abstract

OX40 ligand (OX40L) expressed on APCs, and its receptor, OX40 present on activated T cells, are members of the TNF/TNFR family, respectively, and have been located at the sites of inflammatory conditions. We have observed in OX40L-deficient mice (OX40L-/-) an impaired APC capacity and in our recently constructed transgenic mice expressing OX40L (OX40L-Tg), a markedly enhanced T cell response to protein Ags. Using these mice, we demonstrate here the critical involvement of the OX40L-OX40 interaction during the T cell priming events in the occurrence of experimental autoimmune encephalomyelitis (EAE). In OX40L-/- mice, abortive T cell priming greatly reduced the clinical manifestations of actively induced EAE, coupled with a reduction in IFN-γ, IL-2, and IL-6 production in vitro. Adoptive transfer experiments however revealed an efficient transfer of disease to OX40L-/- mice using wild-type donor T cells, indicating an intact capacity of OX40L-/- mice to initiate effector responses. On the other hand, OX40L-/- donor T cells failed to transfer disease to wild-type recipient mice. Furthermore, OX40L-Tg mice developed a greater severity of EAE despite a delayed onset, while both OX40L-Tg/CD28-/- and OX40L-Tg/CD40-/- mice failed to develop EAE demonstrating a requisite for these molecules. These findings indicate a pivotal role played by OX40L in the pathogenesis of EAE.

Original languageEnglish
Pages (from-to)2991-2999
Number of pages9
JournalJournal of Immunology
Volume167
Issue number5
DOIs
Publication statusPublished - 2001 Sep 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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