Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation.
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.
Matyszak
M K
MK
Department of Biotechnology and Bioscience University of Milano-Bicocca, Milan, Italy.
Denis-Donini
S
S
Citterio
S
S
Longhi
R
R
Granucci
F
F
Ricciardi-Castagnoli
P
P
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D019672:Genes, T-Cell Receptor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006183:H-2 Antigens / Q000032:analysis; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D018122:B7-1 Antigen; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016178:Granulocyte-Macrophage Colony-Stimulating Factor