Dendritic cell maturation overrules H-2D-mediated natural killer T (NKT) cell inhibition: critical role for B7 in CD1d-dependent NKT cell interferon gamma production

J Exp Med. 2001 Oct 15;194(8):1179-86. doi: 10.1084/jem.194.8.1179.

Abstract

Given the broad expression of H-2 class Ib molecules on hematopoietic cells, antigen presentation pathways among CD1d expressing cells might tightly regulate CD1d-restricted natural killer T (NKT) cells. Bone marrow-derived dendritic cells (BM-DCs) and not adherent splenocytes become capable of triggering NK1.1(+)/T cell receptor (TCR)(int) hepatic NKT cell activation when (a) immature BM-DCs lack H-2D(b)-/- molecules or (b) BM-DCs undergo a stress signal of activation. In such conditions, BM-DCs promote T helper type 1 predominant CD1d-restricted NKT cell stimulation. H-2 class Ia-mediated inhibition involves more the direct H-2D(b) presentation than the indirect Qa-1(b) pathway. Such inhibition can be overruled by B7/CD28 interactions and marginally by CD40/CD40L or interleukin 12. These data point to a unique regulatory role of DCs in NKT cell innate immune responses and suggest that H-2 class Ia and Ib pathways differentially control NKT cell recognition of DC antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / genetics
  • Antigens / immunology
  • Antigens, CD1 / genetics
  • Antigens, CD1 / immunology*
  • Antigens, CD1d
  • Antigens, Ly
  • Antigens, Surface
  • B7-1 Antigen / immunology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • CD28 Antigens / immunology
  • Cell Differentiation
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology*
  • Histocompatibility Antigen H-2D
  • Interferon-gamma / biosynthesis*
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily B
  • Proteins / genetics
  • Proteins / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antigens
  • Antigens, CD1
  • Antigens, CD1d
  • Antigens, Ly
  • Antigens, Surface
  • B7-1 Antigen
  • CD28 Antigens
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Klrb1c protein, mouse
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily B
  • Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interferon-gamma