Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells

Eur J Immunol. 2000 Apr;30(4):985-92. doi: 10.1002/(SICI)1521-4141(200004)30:4<985::AID-IMMU985>3.0.CO;2-E.

Abstract

NK T cells produce cytokines when their semi-invariant TCR engages glycolipids associated with CD1d. The physiological consequences of NKT cell activation remain controversial, although they have been implicated in control of autoimmunity, parasites and tumors. We show here that specific activation of NKT cells in liver and spleen leads to a rapid induction of extensive NK cell proliferation and cytotoxicity. This NK cell activation is dependent, at least in part, on IFN-gamma production by NKT cells and IL-12 production by antigen-presenting cells. Remarkably, activation of NK cells by NKT cells is highly selective, since bystander T and B lymphocytes show transient expression of activation markers but almost no proliferation. Collectively our data suggest that CD1d-dependent NKT cells regulate innate immunity by sampling blood-borne glycolipid antigens and rapidly activating NK cells.

MeSH terms

  • Animals
  • Antigens, CD1 / immunology
  • Antigens, CD1 / metabolism
  • Antigens, CD1d
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Cytotoxicity, Immunologic / drug effects
  • Cytotoxicity, Immunologic / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Galactosylceramides / pharmacology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Interleukin-12 / pharmacology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Liver / drug effects
  • Liver / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD1
  • Antigens, CD1d
  • Galactosylceramides
  • Interleukin-12
  • Interferon-gamma