title: CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.
abstract: OBJECTIVE
  Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD.
  
  
  METHODS
  We addressed the function of T cell subsets in KD development by using a well-established murine model of Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis. We determined which T cell subsets were required for development of KD vasculitis by using several knockout murine strains and depleting monoclonal antibodies.
  
  
  RESULTS
  LCWE-injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrates. Frequently, this chronic inflammation resulted in complete occlusion of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. We found that CD8+ T cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for development of KD vasculitis.
  
  
  CONCLUSIONS
  The LCWE-induced murine model of KD vasculitis mimics many histologic features of the disease in humans, such as the presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of KD in humans.
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Magali
authors.initials: M
authors.lastname: Noval Rivas
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Daiko
authors.initials: D
authors.lastname: Wakita
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Norika
authors.initials: N
authors.lastname: Chiba
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Jargalsaikhan
authors.initials: J
authors.lastname: Dagvadorj
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: University of California, Los Angeles.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Hospital for Special Surgery and Weill Medical College of Cornell University, New York, New York.
authors.forename: Thomas J A
authors.initials: TJ
authors.lastname: Lehman
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Crother
authors.affiliation: Cedars-Sinai Medical Center and University of California, Los Angeles.
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
mesh_terms: D000818:Animals; D001167:Arteritis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002457:Cell Extracts / Q000276:immunology*; D002473:Cell Wall; D003324:Coronary Artery Disease / Q000276:immunology*; D004195:Disease Models, Animal; D007780:Lacticaseibacillus casei; D008297:Male; D008810:Mice, Inbred C57BL; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology*
chemical_list: D002457:Cell Extracts