Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation

Eur J Immunol. 1999 Oct;29(10):3063-76. doi: 10.1002/(SICI)1521-4141(199910)29:10<3063::AID-IMMU3063>3.0.CO;2-G.

Abstract

Microglial cells are non-professional antigen-presenting cells (APC) the function of which is still controversial. Here, we studied the function of microglia derived from H-2(u) mice. We show that these microglia express a low level of B7.2 and CD40 and, interestingly, lack surface expression of B7.1. Resting and IFN-gamma-activated microglia were unable to activate naive and primed myelin basic protein (MBP)-specific CD4(+) T cells in the presence of MBP and encephalomyelitic MBP Ac1-11 peptide. Furthermore, in the presence of Ac1-11 peptide, CD4(+) TCR-transgenic T cells became anergized. Microglia became professional APC only after a multistep activation process involving both stimulation through cytokines [granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma] and cognate signaling (B7-CD28 and CD40-CD40 ligand interactions). As such they were able to present MBP to both unprimed and primed T cells. Co-culture of microglia with GM-CSF up-regulated co-stimulatory molecules, in particular B7.1. Additional activation with IFN-gamma induced MHC class II and CD40 up-regulation. CD40-CD40 ligand interaction significantly enhanced microglial ability to prime TCR-transgenic T cells and was essential for presentation of MBP to in vivo primed non-transgenic T cells. We propose that microglia may serve different functions under different inflammatory conditions, depending on the cytokine milieu and the type of cognate interaction they are involved in.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Apoptosis / immunology
  • B7-1 Antigen / biosynthesis
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Cell Division / immunology
  • Clonal Anergy / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism
  • Genes, T-Cell Receptor
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology
  • H-2 Antigens / analysis
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / immunology*
  • Myelin Basic Protein / immunology*
  • Myelin Basic Protein / metabolism
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • B7-1 Antigen
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Myelin Basic Protein
  • Peptide Fragments
  • Granulocyte-Macrophage Colony-Stimulating Factor