TY - JOUR
T1 - Smoking reduces circulating CD26hi CD161hi MAIT cells in healthy individuals and patients with multiple sclerosis
AU - Ammitzbøll, Cecilie
AU - Börnsen, Lars
AU - Romme Christensen, Jeppe
AU - Ratzer, Rikke
AU - Romme Nielsen, Birgitte
AU - Søndergaard, Helle B
AU - von Essen, Marina R
AU - Sellebjerg, Finn
N1 - © Society for Leukocyte Biology.
PY - 2017/5
Y1 - 2017/5
N2 - 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.
AB - 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.
KW - Adult
KW - CD8-Positive T-Lymphocytes/drug effects
KW - Cell Count
KW - Cohort Studies
KW - Cotinine/blood
KW - Dendritic Cells/drug effects
KW - Dipeptidyl Peptidase 4/genetics
KW - Female
KW - Gene Expression Regulation/immunology
KW - Granulocytes/drug effects
KW - Humans
KW - Immunophenotyping
KW - Inducible T-Cell Co-Stimulator Ligand/genetics
KW - Male
KW - Middle Aged
KW - Monocytes/drug effects
KW - Multiple Sclerosis/etiology
KW - NK Cell Lectin-Like Receptor Subfamily B/genetics
KW - Primary Cell Culture
KW - Smoking/adverse effects
U2 - 10.1189/jlb.3a0616-267r
DO - 10.1189/jlb.3a0616-267r
M3 - Journal article
C2 - 28179539
SN - 0741-5400
VL - 101
SP - 1211
EP - 1220
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -