Abstract |
The co-inhibitory B7-homologue 1 (B7-H1/PD-L1) influences adaptive immune responses and has been proposed to contribute to the mechanisms maintaining peripheral tolerance and limiting inflammatory damage in parenchymal organs. To understand the B7-H1/PD1 pathway in CNS inflammation, we analyzed adaptive immune responses in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced EAE and assessed the expression of B7-H1 in human CNS tissue. B7-H1(-/-) mice exhibited an accelerated disease onset and significantly exacerbated EAE severity, although absence of B7-H1 had no influence on MOG antibody production. Peripheral MOG-specific IFN-gamma/IL-17 T cell responses occurred earlier and enhanced in B7-H1(-/-) mice, but ceased more rapidly. In the CNS, however, significantly higher numbers of activated neuroantigen-specific T cells persisted during all stages of EAE. Experiments showing a direct inhibitory role of APC-derived B7-H1 on the activation of MOG-specific effector cells support the assumption that parenchymal B7-H1 is pivotal for delineating T cell fate in the target organ. Compatible with this concept, our data investigating human brain tissue specimens show a strong up-regulation of B7-H1 in lesions of multiple sclerosis. Our findings demonstrate the critical importance of B7-H1 as an immune-inhibitory molecule capable of down-regulating T cell responses thus contributing to the confinement of immunopathological damage.
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Authors | Sonja Ortler, Christoph Leder, Michel Mittelbronn, Alla L Zozulya, Percy A Knolle, Lieping Chen, Antje Kroner, Heinz Wiendl |
Journal | European journal of immunology
(Eur J Immunol)
Vol. 38
Issue 6
Pg. 1734-44
(Jun 2008)
ISSN: 0014-2980 [Print] Germany |
PMID | 18421793
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- B7-1 Antigen
- B7-H1 Antigen
- Cd274 protein, mouse
- Glycoproteins
- Interleukin-17
- MOG protein, human
- Membrane Glycoproteins
- Mog protein, mouse
- Myelin Proteins
- Myelin-Associated Glycoprotein
- Myelin-Oligodendrocyte Glycoprotein
- Peptide Fragments
- Peptides
- myelin oligodendrocyte glycoprotein (35-55)
- Interferon-gamma
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Topics |
- Animals
- Antibody Formation
(immunology)
- Antigen-Presenting Cells
(cytology, immunology, metabolism)
- Antigens, CD
(analysis)
- Apoptosis
(immunology)
- B7-1 Antigen
(immunology)
- B7-H1 Antigen
- Cell Count
- Central Nervous System
(immunology, metabolism, pathology)
- Disease Models, Animal
- Glycoproteins
(immunology)
- Humans
- Interferon-gamma
(metabolism)
- Interleukin-17
(metabolism)
- Kinetics
- Lymphocyte Activation
(immunology)
- Membrane Glycoproteins
(immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Multiple Sclerosis
(immunology, metabolism, pathology)
- Myelin Proteins
- Myelin-Associated Glycoprotein
(immunology)
- Myelin-Oligodendrocyte Glycoprotein
- Peptide Fragments
(immunology)
- Peptides
(immunology)
- Spleen
(cytology, immunology)
- T-Lymphocyte Subsets
(cytology, immunology, metabolism)
- T-Lymphocytes
(cytology, immunology, metabolism)
- Vaccination
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