CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.

Research output: Contribution to journalArticle

Abstract

The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show that CD1-/- mice develop a clinically more severe and chronic EAE compared with CD1+/+ C57BL/6 mice, which was histopathologically confirmed with increased demyelination and CNS infiltration in CD1-/- mice. Autoantigen rechallenge in vitro revealed similar T cell proliferation in CD1+/+ and CD1-/- mice but an amplified cytokine response in CD1-/- mice as measured by both the Th1 cytokine IFN-{gamma} and the Th2 cytokine IL-4. Investigation of cytokine production at the site of inflammation showed a CNS influx of TGF-{beta}1-producing cells early in the disease in CD1+/+ mice, which was absent in the CD1-/- mice. Passive transfer of EAE using an autoreactive T cell line induced equivalent disease in both groups, which suggested additional requirements for activation of the CD1-dependent regulatory pathway(s). When immunized with CFA before T cell transfer, the CD1-/- mice again developed an augmented EAE compared with CD1+/+ mice. We suggest that CD1 exerts its function during CFA-mediated activation, regulating development of EAE both through enhancing TGF-{beta}1 production and through limiting autoreactive T cell activation, but not necessarily via effects on the Th1/Th2 balance.

Details

Authors
  • Anna Teige
  • Ingrid Teige
  • Shahram Lavasani
  • Robert Bockermann
  • Emma Mondoc
  • Rikard Holmdahl
  • Shohreh Issazadeh-Navikas
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)186-194
JournalJournal of Immunology
Volume172
Issue number1
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Animal Physiology (Closed 2011) (011011000), Functional Zoology (432112239), Immunology (013212020)

Related research output

Teige, A., 2014, Department of Clinical Sciences, Lund University. 59 p.

Research output: ThesisDoctoral Thesis (compilation)

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