Immunization with alpha-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesis

Eur J Immunol. 1999 Jun;29(6):2014-25. doi: 10.1002/(SICI)1521-4141(199906)29:06<2014::AID-IMMU2014>3.0.CO;2-G.

Abstract

We have compared the immune responses of mice immunized either with alpha-galactosylceramide (alpha-GalCer), capable of eliciting a CD1-metiated stimulation of V alpha14+ NK T cells, or with lipoarabinomannan (LAM), a glycophospholipid derived from mycobacteria which is known to be presented by CD1b in humans. Within 24 h, alpha-GalCer induces a burst of IFN-gamma secretion in vivo, and recall with antigen in vitro leads to the synthesis of IL-4 and IL-10 in addition to IFN-gamma. Associated with this in vivo cytokine release is a polyclonal activation of splenic B and T cells. CD1-reactive NK T lymphocytes mediate these events, because none of them are observed in alpha-GalCer-immunized CD1-/- mice. LAM immunization fails to promote similar early responses in vivo. Repeated exposure of mice to alpha-GalCer induces splenic T cells to secrete IL-4 and IL-10 but dramatically reduced levels of IFN-gamma. Such a bias in the cytokine balance triggered by NK T cells stimulated with multiple doses of alpha-GalCer suggests that this compound might be useful in the induction of Th2 immune responses and the prevention of chronic inflammatory conditions mediated by Th1 cytokines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, CD1 / genetics
  • Antigens, CD1 / metabolism
  • Cytokines / biosynthesis*
  • Galactosylceramides / immunology*
  • Immunization
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Killer Cells, Natural / immunology*
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Antigens, CD1
  • Cytokines
  • Galactosylceramides
  • Lipopolysaccharides
  • lipoarabinomannan
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma