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.
abstract: BACKGROUND
  CD4(+) CD25(+) forkhead box P3 (FoxP3)(+) regulatory T cells (T reg cells) are known to suppress adaptive immune responses, key control tolerance and autoimmunity.
  
  
  METHODS
  We challenged the role of CD4(+) T reg cells in suppressing established CD8(+) T effector cell responses by using the OT-I/II system in vitro and an OT-I-mediated, oligodendrocyte directed ex vivo model (ODC-OVA model).
  
  
  RESULTS
  CD4(+) T reg cells dampened cytotoxicity of an ongoing CD8(+) T effector cell attack in vitro and within intact central nervous system tissue ex vivo. However, their suppressive effect was limited by the strength of the antigen signal delivered to the CD8(+) T effector cells and the ratio of regulatory to effector T cells. CD8(+) T effector cell suppression required T cell receptor-mediated activation together with costimulation of CD4(+) T reg cells, but following activation, suppression did not require restimulation and was antigen non-specific.
  
  
  CONCLUSIONS
  Our results suggest that CD4(+) T reg cells are capable of suppressing CD8(+) T effector cell responses at the parenchymal site, that is, limiting parenchymal damage in autoimmune central nervous system inflammation.
authors.affiliation: Department of Neurology - Inflammatory Disorders of the Nervous System and Neurooncology, University of Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Göbel
authors.forename: Stefan
authors.initials: S
authors.lastname: Bittner
authors.forename: Nico
authors.initials: N
authors.lastname: Melzer
authors.forename: Susann
authors.initials: S
authors.lastname: Pankratz
authors.forename: Angela
authors.initials: A
authors.lastname: Dreykluft
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schuhmann
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics; D009836:Oligodendroglia / Q000187:drug effects; D009924:Organ Culture Techniques; D009930:Organic Chemicals / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000187:drug effects / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D004676:Myelin Basic Protein; C110366:OVA-8; D009930:Organic Chemicals; C070080:PKH 26; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase