Smoking reduces circulating CD26hiCD161hiMAIT cells in healthy individuals and patients with multiple sclerosis.
Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI). In addition, we analyzed immune cell subsets associated with smoking in 2 independent cohorts of patients with MS. In HI smokers compared with nonsmokers, we found increased blood cell counts of granulocytes, monocytes, and lymphocytes. These cells were not more proinflammatory, autoreactive, or EBV reactive compared with cells from nonsmokers. Phenotypic differences were seen in plasmacytoid dendritic cells (pDCs) and CD8+T cells as higher percentages of ICOS ligand (ICOSL)+pDCs and lower percentages of CD26hiCD161hiCD8+T cells and CCR6+CD8+T cells in smokers compared with nonsmokers. In supplemental analyses, we showed that CD26hiCD161hiCD8+T cells were mainly mucosal-associated invariant T cells (MAITs). Comparable frequencies of ICOSL+pDCs, CCR6+CD8+T cells, and CD26hiCD161hiCD8+T cells were found between HI and MS patients who were nonsmokers. Our findings suggest general proinflammatory effects from smoking combined with skewing of specific cell populations in HI and MS patients. The function of these cell populations needs further investigation.
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark cecilie.ammitzboell@regionh.dk.
Cecilie
C
Ammitzbøll
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Lars
L
Börnsen
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jeppe
J
Romme Christensen
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Rikke
R
Ratzer
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Birgitte
B
Romme Nielsen
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Helle B
HB
Søndergaard
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Marina R
MR
von Essen
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Finn
F
Sellebjerg
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D012907:Smoking / Q000009:adverse effects / Q000235:genetics / Q000276:immunology* / Q000473:pathology
C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D003367:Cotinine
CCR6; CD8; ICOSL; T cell; pDC