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

Malgosia K. Matyszak, Suzanne Denis-Donini, Stefania Citterio, Renato Longhi, Francesca Granucci, Paola Ricciardi-Castagnoli

Research output: Contribution to journalArticle

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 87.2 and CD40 and, interestingly, lack surface expression of 87.1. Resting and IFN-γ-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-γ] 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-γ 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.

Original languageEnglish
Pages (from-to)3063-3076
Number of pages14
JournalEuropean Journal of Immunology
Volume29
Issue number10
DOIs
Publication statusPublished - 1999

Keywords

  • Anergy
  • Antigen presentation
  • Co-stimulation
  • Microglia
  • Myelin basic protein

ASJC Scopus subject areas

  • Immunology

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