B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage: implications for the lesion pathogenesis of multiple sclerosis.

Publikation: Beiträge in ZeitschriftenZeitschriftenaufsätzeForschung

Authors

  • Sonja Ortler
  • Christoph Leder
  • Michel Mittelbronn
  • Alla L. Zozulya
  • Percy A. Knolle
  • Antje Kroner
  • Heinz Wiendl
  • Lieping Chen

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-γ/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.

Titel in ÜbersetzungB7-H1 schränkt Neuroantigen-spezifische T Zellantworten ein und begrenzt entzündlichen CNS-Schaden: Folgen für die Läsionspathogenese multipler Sklerose.
OriginalspracheEnglisch
ZeitschriftEuropean Journal of Immunology
Jahrgang38
Ausgabenummer6
Seiten (von - bis)1734-1744
Anzahl der Seiten11
ISSN0014-2980
DOIs
PublikationsstatusErschienen - 06.2008
Extern publiziertJa

DOI