title: Immunomodulatory strategies prevent the development of autoimmune emphysema.
abstract: BACKGROUND
  The presence of anti-endothelial cell antibodies and pathogenic T cells may reflect an autoimmune component in the pathogenesis of emphysema. Whether immune modulatory strategies can protect against the development of emphysema is not known.
  
  
  METHODS
  Sprague Dawley rats were immunized with human umbilical vein endothelial cells (HUVEC) to induce autoimmune emphysema and treated with intrathymic HUVEC-injection and pristane. Measurements of alveolar airspace enlargement, cytokine levels, immuno histochemical, western blot analysis, and T cell repertoire of the lung tissue were performed.
  
  
  RESULTS
  The immunomodulatory strategies protected lungs against cell death as demonstrated by reduced numbers of TUNEL and active caspase-3 positive cells and reduced levels of active caspase-3, when compared with lungs from HUVEC-immunized rats. Immunomodulatory strategies also suppressed anti-endothelial antibody production and preserved CNTF, IL-1alpha and VEGF levels. The immune deviation effects of the intrathymic HUVEC-injection were associated with an expansion of CD4+CD25+Foxp3+ regulatory T cells. Pristane treatment decreased the proportion of T cells expressing receptor beta-chain, Vβ16.1 in the lung tissue.
  
  
  CONCLUSIONS
  Our data demonstrate that interventions classically employed to induce central T cell tolerance (thymic inoculation of antigen) or to activate innate immune responses (pristane treatment) can prevent the development of autoimmune emphysema.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hanaoka
authors.forename: Mark R
authors.initials: MR
authors.lastname: Nicolls
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
authors.forename: Donatas
authors.initials: D
authors.lastname: Kraskauskas
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mack
authors.forename: Adelheid
authors.initials: A
authors.lastname: Kratzer
authors.forename: Jonas
authors.initials: J
authors.lastname: Salys
authors.forename: Vita
authors.initials: V
authors.lastname: Kraskauskiene
authors.forename: Nana
authors.initials: N
authors.lastname: Burns
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Voelkel
authors.forename: Laimute
authors.initials: L
authors.lastname: Taraseviciene-Stewart
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control*; D015551:Autoimmunity / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004646:Emphysema / Q000276:immunology* / Q000517:prevention & control*; D056747:Immunomodulation / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines