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Microglia induce myelin basic protein‐specific T cell anergy or T cell activation, according to their state of activation
Author(s) -
Matyszak Malgosia K.,
DenisDonini Suzanne,
Citterio Stefania,
Longhi Renato,
Granucci Francesca,
RicciardiCastagnoli Paola
Publication year - 1999
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/(sici)1521-4141(199910)29:10<3063::aid-immu3063>3.0.co;2-g
Subject(s) - microglia , cd40 , biology , microbiology and biotechnology , myelin basic protein , t cell , cd28 , antigen presentation , antigen presenting cell , mhc class ii , immunology , cytotoxic t cell , myelin , immune system , inflammation , neuroscience , in vitro , biochemistry , central nervous system
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‐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.