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Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity
F Dangond1, A Windhagen, C J Groves
1Laboratory of Molecular Immunology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Abstract:
Human microglia constitute the primary residential antigen presenting cells (APCs) in the central nervous system (CNS) and have the capacity of activating myelin reactive T-cells. T-cell activation requires two signals: first is the interaction of the T-cell receptor with the MHC-antigen complex and, secondly, contact of the CD28/CTLA4 T-cell surface molecules with the B7 family of costimulatory molecules on the APCs. We have previously shown high expression of B7.1 in early multiple sclerosis (MS) plaques, suggesting that acute T-cell-mediated CNS inflammation may require local B7.1 upregulation. We have now examined the expression of B7.1 and B7.2 costimulatory molecules on resting ex-vivo human microglia isolated directly from biopsy specimens. We found constitutive expression of B7.2 but not B7.1 on resting microglia, suggesting that B7.2 expression may lead to downregulation of pro-inflammatory Th1 T-cell responses in the normal brain.
Insights
Resting human microglia express B7.2, a molecule that may downregulate inflammatory T-cell responses in the brain. This contrasts with B7.1, which is upregulated in multiple sclerosis (MS).
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- Human microglia are key antigen-presenting cells (APCs) in the central nervous system (CNS).
- T-cell activation requires co-stimulatory signals from APCs, involving molecules like B7.1 and B7.2.
- Previous work indicated B7.1 upregulation in early multiple sclerosis (MS) lesions.
Purpose of the Study:
- To investigate the expression of B7.1 and B7.2 costimulatory molecules on resting human microglia.
- To understand the role of these molecules in CNS immune responses.
Main Methods:
- Isolation of resting ex-vivo human microglia from biopsy specimens.
- Analysis of B7.1 and B7.2 expression on these microglia.
Main Results:
- Resting human microglia constitutively express B7.2.
- B7.1 expression was not detected on resting microglia.
- This suggests a potential role for B7.2 in regulating T-cell responses in the normal brain.
Conclusions:
- Resting microglia express B7.2, potentially dampening pro-inflammatory Th1 T-cell responses.
- The absence of B7.1 on resting microglia suggests its upregulation is specific to inflammatory conditions like MS.