title: T-cell activation and HLA-regulated response to smoking in the deep airways of patients with multiple sclerosis.
abstract: Cigarette smoking is a risk factor for multiple sclerosis (MS), and the risk is further multiplied for HLA-DRB1*15(+) smokers. To define the smoke-induced immune responses in the lung we performed bronchoscopy with bronchoalveolar lavage (BAL) on smokers and non-smokers, both MS-patients and healthy volunteers. In the BAL, non-smokers with MS showed an increased preformed CD40L expression in CD4(+) T-cells while smokers displayed an increase in proliferating (Ki-67(+)) T-cells. In addition, our results confirm that smoking induces an increase of alveolar macrophages in BAL, and further defined a significant attenuation of this response in carriers of the HLA-DRB1*15 allele, in both MS patients and healthy controls. This first systematic investigation of the immune response in the lungs of smokers and non-smokers diagnosed with MS, thus suggests an MS-associated lung T-cell phenotype, involvement of a specific T-cell response to smoke, and a genetic regulation of the macrophage response.
authors.affiliation: Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Electronic address: johan.ockinger@ki.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Öckinger
authors.affiliation: Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Hagemann-Jensen
authors.affiliation: Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Lung Allergy Clinic, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Kullberg
authors.affiliation: Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Benita
authors.initials: B
authors.lastname: Engvall
authors.affiliation: Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Lung Allergy Clinic, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.affiliation: Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Lung Allergy Clinic, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Wahlström
mesh_terms: D000328:Adult; D000483:Alleles; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D016014:Linear Models; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012307:Risk Factors; D012907:Smoking / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; D019394:Ki-67 Antigen; D023201:CD40 Ligand