Göbel, Kerstin;
Bittner, Stefan;
Melzer, Nico;
Pankratz, Susann;
Dreykluft, Angela;
Schuhmann, Michael K;
Meuth, Sven G;
Wiendl, Heinz
CD4+ CD25+ FoxP3+ regulatory T cells suppress cytotoxicity of CD8+ effector T cells: implications for their capacity to limit inflammatory central nervous system damage at the parenchymal level
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Media type:
E-Article
Title:
CD4+ CD25+ FoxP3+ regulatory T cells suppress cytotoxicity of CD8+ effector T cells: implications for their capacity to limit inflammatory central nervous system damage at the parenchymal level
Contributor:
Göbel, Kerstin;
Bittner, Stefan;
Melzer, Nico;
Pankratz, Susann;
Dreykluft, Angela;
Schuhmann, Michael K;
Meuth, Sven G;
Wiendl, Heinz
imprint:
Springer Science and Business Media LLC, 2012
Published in:Journal of Neuroinflammation
Language:
English
DOI:
10.1186/1742-2094-9-41
ISSN:
1742-2094
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>CD4<jats:sup>+</jats:sup>CD25<jats:sup>+</jats:sup>forkhead box P3 (FoxP3)<jats:sup>+</jats:sup>regulatory T cells (T reg cells) are known to suppress adaptive immune responses, key control tolerance and autoimmunity.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We challenged the role of CD4<jats:sup>+</jats:sup>T reg cells in suppressing established CD8<jats:sup>+</jats:sup>T effector cell responses by using the OT-I/II system<jats:italic>in vitro</jats:italic>and an OT-I-mediated, oligodendrocyte directed<jats:italic>ex vivo</jats:italic>model (ODC-OVA model).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>CD4<jats:sup>+</jats:sup>T reg cells dampened cytotoxicity of an ongoing CD8<jats:sup>+</jats:sup>T effector cell attack<jats:italic>in vitro</jats:italic>and within intact central nervous system tissue<jats:italic>ex vivo</jats:italic>. However, their suppressive effect was limited by the strength of the antigen signal delivered to the CD8<jats:sup>+</jats:sup>T effector cells and the ratio of regulatory to effector T cells. CD8<jats:sup>+</jats:sup>T effector cell suppression required T cell receptor-mediated activation together with costimulation of CD4<jats:sup>+</jats:sup>T reg cells, but following activation, suppression did not require restimulation and was antigen non-specific.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our results suggest that CD4<jats:sup>+</jats:sup>T reg cells are capable of suppressing CD8<jats:sup>+</jats:sup>T effector cell responses at the parenchymal site, that is, limiting parenchymal damage in autoimmune central nervous system inflammation.</jats:p></jats:sec>