T-cell activation and HLA-regulated response to smoking in the deep airways of patients with multiple sclerosis

Clin Immunol. 2016 Aug:169:114-120. doi: 10.1016/j.clim.2016.06.006. Epub 2016 Jun 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoscopy
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • Female
  • Flow Cytometry
  • HLA-DRB1 Chains / genetics
  • HLA-DRB1 Chains / immunology*
  • Humans
  • Ki-67 Antigen / immunology
  • Ki-67 Antigen / metabolism
  • Linear Models
  • Lung / immunology*
  • Lung / metabolism
  • Lung / physiopathology
  • Lymphocyte Activation / immunology
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Risk Factors
  • Smoking / genetics
  • Smoking / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • HLA-DRB1 Chains
  • Ki-67 Antigen
  • CD40 Ligand