title: An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells.
abstract: OBJECTIVE
  Activation of the sympathetic nervous system (SNS) ameliorates collagen-induced arthritis (CIA) in the late phase of the disease but aggravates it in the presymptomatic phase. The aim of the present study was to determine whether CD4+CD25+ T cells are influenced by the SNS of mice and play a disease-modifying role in the early symptomatic phase of the disease.
  
  
  METHODS
  We tested the effects of the SNS on arthritis by transferring CD4+CD25+ T cells from sympathectomized mice immunized with type II collagen and from immunized, SNS-intact animals (controls). We further characterized transferred cells by studying forkhead box P3 (FoxP3) expression, cell proliferation, and cytokine secretion.
  
  
  RESULTS
  Using anti-dopamine-beta-hydroxylase antibodies for systemic sympathectomy, we noticed a time-dependent disease amelioration (strongest when sympathectomy was performed 7 days before immunization, with no effect 30 days after immunization). When CD4+CD25+ T cells from immunized and sympathectomized animals were transferred into mice with CIA (on day 32), disease severity was reduced compared with that in controls. However, the number of CD4+CD25+FoxP3+ cells and the FoxP3 expression level in CD4+CD25+ cells were not changed by sympathectomy. In a mixed assay of donor CD4+CD25- and CD4+CD25+ cells, proliferation was reduced when cells from sympathectomized animals were studied. In the same assay, secretion of tumor necrosis factor, interleukin-17 (IL-17), IL-10, and IL-4 (not interferon-gamma) was markedly reduced when cells were taken from sympathectomized animals. Culture of CD4+CD25+ cells with norepinephrine (10(-5)M) for 24 hours before transfer worsened the arthritis.
  
  
  CONCLUSIONS
  The SNS increases disease severity in the early phase of symptomatic CIA by stimulating several proinflammatory aspects of CD4+CD25+ T cells.
authors.affiliation: University Hospital Regensburg, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Härle
authors.forename: Georg
authors.initials: G
authors.lastname: Pongratz
authors.forename: Julia
authors.initials: J
authors.lastname: Albrecht
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Tarner
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D053264:B-Cell Activating Factor / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D051379:Mice; D008811:Mice, Inbred DBA; D009638:Norepinephrine / Q000494:pharmacology; D012720:Severity of Illness Index; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013566:Sympathomimetics / Q000494:pharmacology
chemical_list: D053264:B-Cell Activating Factor; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D013566:Sympathomimetics; D009638:Norepinephrine