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The costimulatory molecule B7 is expressed on human microglia in culture and in multiple sclerosis acute lesions
R De Simone1, A Giampaolo, B Giometto
1Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
Insights
B7 costimulatory molecule expression on microglia is key for T cell activation in the brain. This molecule is upregulated by interferon-gamma and implicated in multiple sclerosis lesion development.
Area of Science:
- Neuroimmunology
- Cellular Immunology
- Molecular Biology
Background:
- B7 is a critical costimulatory molecule for T cell activation.
- Intracerebral immune responses involve complex cellular interactions.
- Microglia are the primary immune cells in the central nervous system.
Purpose of the Study:
- To investigate the expression and regulation of B7 molecule in human microglial cells.
- To determine the role of B7 in the context of multiple sclerosis brain tissue.
Main Methods:
- Immunocytochemistry and polymerase chain reaction (PCR) were used to detect B7 expression.
- Cultured human embryonic microglia and brain tissue sections from multiple sclerosis patients were analyzed.
- Binding assays with CTLA-4-Ig and anti-B7 antibodies were performed.
Main Results:
- B7 was expressed in cultured human microglia and upregulated by interferon-gamma.
- Microglia, but not astrocytes, expressed B7 and bound CTLA-4-Ig.
- B7 immunoreactivity was found on activated microglia and macrophages in active multiple sclerosis lesions.
Conclusions:
- B7 expression on microglia suggests a role in T cell activation within the central nervous system.
- Regulated B7 expression on microglia may contribute to T cell proliferation and effector functions in multiple sclerosis.
- B7 is implicated in the pathogenesis of multiple sclerosis lesions.
Abstract:
B7 is a costimulatory molecule which is expressed on antigen-presenting cells and which plays a pivotal role in T cell activation and proliferation. To elucidate mechanisms regulating intracerebral immune responses, expression of B7 was examined in cultured microglial cells and in brain tissue from control and multiple sclerosis patients. Using immunocytochemical and polymerase chain reaction techniques, we show that B7 was expressed in cultured microglial cells from the human embryonic brain. Microglia also bound the soluble form of the B7 receptor CTLA-4 (CTLA-4-Ig). B7 gene expression and binding of anti-B7 antibodies and CTLA-4-Ig increased after treatment with interferon-gamma. B7 was not inducible in human astrocytes. Human microglia expressed other costimulatory molecules, such as intercellular adhesion molecule-1, LFA-1 and LFA-3. In sections of multiple sclerosis brains, B7 immunoreactivity was detected on activated microglia and infiltrating macrophages within active lesions. In chronic lesions, only perivascular cells were stained. B7 immunoreactivity was undetectable in sections from Alzheimer's disease or normal brain tissue. These data suggest that B7 may be involved in T cell activation and lesion development in multiple sclerosis and that the regulated expression of B7 on microglia may contribute to the local stimulation of T cell proliferation and effector functions.