| First Author | Ortler S | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 6 | Pages | 1734-44 |
| PubMed ID | 18421793 | Mgi Jnum | J:136302 |
| Mgi Id | MGI:3795845 | Doi | 10.1002/eji.200738071 |
| Citation | Ortler S, et al. (2008) B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage: Implications for the lesion pathogenesis of multiple sclerosis. Eur J Immunol 38(6):1734-44 |
| abstractText | 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. |
