title: Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.
abstract: BACKGROUND
  Numbers of CD8(+) T cells expressing the leukotriene B4 (LTB4) receptor, BLT1, have been correlated with asthma severity.
  
  
  OBJECTIVE
  To examine the activation and numbers of BLT1-expressing peripheral blood CD4(+) and CD8(+) T cells from patients with steroid-sensitive (SS) and steroid-resistant (SR) asthma.
  
  
  METHODS
  CD4(+) and CD8(+) T cells isolated from peripheral blood of healthy human subjects and patients with SS and SR asthma were stimulated in culture with anti-CD3/anti-CD28 followed by analysis of BLT1 surface expression and cytokine production. Activation of CD8(+) T cells after ligation of BLT1 by LTB4 was monitored by changes in intracellular Ca(2+) concentrations.
  
  
  RESULTS
  The number of BLT1-expressing cells was larger in patients with asthma than in controls and larger on activated CD8(+) than on CD4(+) T cells. Addition of LTB4 to activated CD8(+) T cells resulted in increases in intracellular Ca(2+) concentrations. Expansion of activated CD4(+) T cells, unlike CD8(+) T cells, was significantly decreased in the presence of corticosteroid. In patients with SS asthma, numbers of BLT1-expressing CD8(+) T cells were lower in the presence of corticosteroid, unlike in those with SR asthma in whom cell expansion was maintained. Levels of interleukin-13 were highest in cultured CD8(+) T cells, whereas interleukin-10 levels were higher in CD4(+) T cells from controls and patients with SS asthma. Interferon-γ levels were lowest in patients with SR asthma.
  
  
  CONCLUSIONS
  Differences in BLT1 expression, steroid sensitivity, and cytokine production were demonstrated in T lymphocytes from patients with SS and SR asthma. The LTB4-BLT1 pathway in CD8(+) cells may play an important role in asthma and serve as an important target in the treatment of patients with SR asthma.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Chung
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Division of Allergy, Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado.
authors.forename: E Rand
authors.initials: ER
authors.lastname: Sutherland
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado. Electronic address: gelfande@njhealth.org.
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D018102:Receptors, Leukotriene B4 / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D017077:Culture Media, Conditioned; C508609:IL10 protein, human; D018793:Interleukin-13; C513240:LTB4R protein, human; D018102:Receptors, Leukotriene B4; D016753:Interleukin-10; D003907:Dexamethasone; D007371:Interferon-gamma; D002118:Calcium