@article{CochainChaudhariKochetal.2014,
  author    = {Cochain, Clement and Chaudhari, Sweena M. and Koch, Miriam and Wiendl, Heinz and Eckstein, Hans-Henning and Zernecke, Alma},
  title     = {Programmed Cell Death-1 Deficiency Exacerbates T Cell Activation and Atherogenesis despite Expansion of Regulatory T Cells in Atherosclerosis-Prone Mice},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {4},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0093280},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119823},
  pages     = {e93280},
  year      = {2014},
  abstract  = {T cell activation represents a double-edged sword in atherogenesis, as it promotes both pro-inflammatory T cell activation and atheroprotective Foxp3(+) regulatory T cell (Treg) responses. Here, we investigated the role of the co-inhibitory receptor programmed cell death-1 (PD-1) in T cell activation and CD4(+) T cell polarization towards pro-atherogenic or atheroprotective responses in mice. Mice deficient for both low density lipoprotein receptor and PD-1 (Ldlr(-/-)Pd1(-/-)) displayed striking increases in systemic CD4(+) and CD8(+) T cell activation after 9 weeks of high fat diet feeding, associated with an expansion of both pro-atherogenic IFNγ-secreting T helper 1 cells and atheroprotective Foxp3+ Tregs. Importantly, PD-1 deficiency did not affect Treg suppressive function in vitro. Notably, PD-1 deficiency exacerbated atherosclerotic lesion growth and entailed a massive infiltration of T cells in atherosclerotic lesions. In addition, aggravated hypercholesterolemia was observed in Ldlr(-/-)Pd1(-/-) mice. In conclusion, we here demonstrate that although disruption of PD-1 signaling enhances both pro- and anti-atherogenic T cell responses in Ldlr(-/-) mice, pro-inflammatory T cell activation prevails and enhances dyslipidemia, vascular inflammation and atherosclerosis.},
  language  = {en}
}
@article{MeyerzuHoersteCordesMausbergetal.2014,
  author    = {Meyer zu H{\"o}rste, Gerd and Cordes, Steffen and Mausberg, Anne K. and Zozulya, Alla L. and Wessig, Carsten and Sparwasser, Tim and Mathys, Christian and Wiendl, Heinz and Hartung, Hans-Peter and Kieseier, Bernd C.},
  title     = {FoxP3+Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0108756},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115239},
  pages     = {e108756},
  year      = {2014},
  abstract  = {Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies.},
  language  = {en}
}