title: Roles of CRTH2+ CD4+ T cells in immunoglobulin G4-related lacrimal gland enlargement.
abstract: BACKGROUND
  Lacrimal gland enlargement (LGE) is one of the characteristics of Mikulicz's disease (MD). Recently, marked serum immunoglobulin (Ig)G4 elevation and infiltration of IgG4-positive plasma cells in the enlarged exocrine glands have been reported in MD patients. Moreover, we have reported that in patients with LGE and elevated serum IgG4 levels (IgG4-related LGE), T helper type 2 (Th2) cell-mediated immune responses are enhanced. Although prostaglandin D2 (PGD2) and its receptor CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) have been shown to be involved in Th2 cell-related diseases such as bronchial asthma, their roles in IgG4-related diseases remain unknown.
  
  
  OBJECTIVE
  The aim of this study is to address the role of CD4+ T cells expressing CRTH2 (CRTH2+ CD4+ T cells) in IgG4-related LGE.
  
  
  METHODS
  We examined the expression of CCR4, CXCR3 and CRTH2 on peripheral blood CD4+ T cells in patients with IgG4-related LGE, in patients with bronchial asthma and in healthy controls.
  
  
  RESULTS
  The ratio of CCR4+ to CXCR3+ in CD45RO+ CD4+ T cells was increased in patients with IgG4-related LGE when compared to that in healthy controls, confirming that Th2 cells are predominant in patients with IgG4-related LGE. In addition, the frequency of CRTH2+ cells in CD4+ T cells was significantly increased in these patients, compared to healthy controls. Furthermore, although not statistically significant, the frequency of CRTH2+ cells in CD4+ T cells tended to correlate with the levels of serum IgE and the number of blood eosinophils in patients with IgG4-related LGE.
  
  
  CONCLUSIONS
  CRTH2+ CD4+ T cells may be involved in the pathogenesis of IgG4-related LGE.
authors.affiliation: Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Saito
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kagami
authors.forename: Saki
authors.initials: S
authors.lastname: Kawashima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Oshitari
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007766:Lacrimal Apparatus Diseases / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4 / Q000276:immunology; D054367:Receptors, CXCR3 / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D011982:Receptors, Prostaglandin / Q000276:immunology*
chemical_list: C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D007074:Immunoglobulin G; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor