Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide

Research output: Contribution to journalArticle

Abstract

Class I and class II MHC-restricted T cells specific for proteins present in myelin have been shown to be involved in autoimmunity in the central nervous system (CNS). It is not yet known whether CD1d-restricted T cells reactive to myelin-derived lipids are present in the CNS and might be targeted to influence the course of autoimmune demyelination. Using specific glycohpid-CD1d tetramers and cloned T cells we have characterized a T cell population reactive to a myelin-derived glycolipid, sulfatide, presented by CD1 d. This population is distinct from the invariant Valpha14(+) NK T cells, and a panel of Valpha3/Valpha8(+) CD1d-restricted NK T cell hybridomas is unable to recognize sulfatide in the presence of CD1d(+) antigen-presenting cells. Interestingly, during experimental autoimmune encephalomyelitis a model for human multiple sclerosis, sulfatide-reactive T cells but not invariant NK T cells are increased severalfold in CNS tissue. Moreover, treatment of mice with sulfatide prevents antigen-induced experimental autoimmune encephalomyelitis in wild-type but not in CD1d-deficient mice. Disease prevention correlates with the ability of sulfatide to suppress both interferon-gamma and interleukin-4 production by pathogenic myelin oligodendrocyte glycoprotein-reactive T cells. Since recognition of sulfatide by CD1d-restricted T cells has now been shown both in mice and humans, study of murine myelin lipid-reactive T cells may form a basis for the development of intervention strategies in human autoimmune demyelinating diseases.

Details

Authors
  • A Jahng
  • I Maricic
  • C Aguilera
  • Susanna Cardell
  • RC Halder
  • V Kumar
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • glycolipids, NK T cells, EAE, sulfatides, CD1d
Original languageEnglish
Pages (from-to)947-957
JournalJournal of Experimental Medicine
Volume199
Issue number7
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes