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 language | English |
|---|---|
| Pages (from-to) | 3063-3076 |
| Number of pages | 14 |
| Journal | European Journal of Immunology |
| Volume | 29 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 1999 |
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Keywords
- Anergy
- Antigen presentation
- Co-stimulation
- Microglia
- Myelin basic protein
ASJC Scopus subject areas
- Immunology
Cite this
Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation. / Matyszak, Malgosia K.; Denis-Donini, Suzanne; Citterio, Stefania; Longhi, Renato; Granucci, Francesca; Ricciardi-Castagnoli, Paola.
In: European Journal of Immunology, Vol. 29, No. 10, 1999, p. 3063-3076.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation
AU - Matyszak, Malgosia K.
AU - Denis-Donini, Suzanne
AU - Citterio, Stefania
AU - Longhi, Renato
AU - Granucci, Francesca
AU - Ricciardi-Castagnoli, Paola
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Anergy
KW - Antigen presentation
KW - Co-stimulation
KW - Microglia
KW - Myelin basic protein
UR - http://www.scopus.com/inward/record.url?scp=0032872925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032872925&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1521-4141(199910)29:10<3063::AID-IMMU3063>3.0.CO;2-G
DO - 10.1002/(SICI)1521-4141(199910)29:10<3063::AID-IMMU3063>3.0.CO;2-G
M3 - Article
C2 - 10540317
AN - SCOPUS:0032872925
VL - 29
SP - 3063
EP - 3076
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 10
ER -