Role of costimulation in the induction of the IL-12/IL-12 receptor pathway and the development of autoimmunity

J Immunol. 2000 Jan 1;164(1):100-6. doi: 10.4049/jimmunol.164.1.100.

Abstract

Costimulation mediated by the interactions of the B7 Ags (CD80/CD86) on APC with CD28 on the responding T cell regulates the magnitude of the immune response and may influence Th1/Th2 development. The IL-12Rbeta2 subunit plays a critical role in maintaining IL-12 responsiveness and controlling Th1 lineage commitment. We demonstrate that IL-2 and IL-12 resulting from CD28/B7 interactions both play a critical role in the induction of expression of the IL-12Rbeta2 subunit and as a result the differentiation of pathogenic autoreactive effector cells. These findings suggest that targeting IL-2 and IL-12 simultaneously may be effective in the treatment of Th1-mediated autoimmunity.

MeSH terms

  • Abatacept
  • Adjuvants, Immunologic / physiology
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / pharmacology
  • B7-1 Antigen / physiology*
  • CD28 Antigens / genetics
  • CD28 Antigens / physiology*
  • CD40 Antigens / metabolism
  • CD40 Ligand
  • CTLA-4 Antigen
  • Cell Differentiation / immunology
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Immunoconjugates*
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / pharmacology
  • Interleukin-12 / physiology
  • Interleukin-2 / physiology
  • Ligands
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Receptors, Interleukin / biosynthesis*
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-12
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • CD28 Antigens
  • CD40 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Interleukin-2
  • Ligands
  • Membrane Glycoproteins
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • CD40 Ligand
  • Interleukin-12
  • Abatacept
  • Interferon-gamma