Smoking reduces circulating CD26hi CD161hi MAIT cells in healthy individuals and patients with multiple sclerosis

Cecilie Ammitzbøll; Lars Börnsen; Jeppe Romme Christensen; Rikke Ratzer; Birgitte Romme Nielsen; Helle B Søndergaard; Marina R von Essen; Finn Sellebjerg

doi:10.1189/jlb.3a0616-267r

Smoking reduces circulating CD26^hi CD161^hi MAIT cells in healthy individuals and patients with multiple sclerosis

Cecilie Ammitzbøll, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Birgitte Romme Nielsen, Helle B Søndergaard, Marina R von Essen, Finn Sellebjerg

Department of Clinical Medicine

14 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Leukocyte Biology
Volume	101
Issue number	5
Pages (from-to)	1211-1220
ISSN	0741-5400
DOIs	https://doi.org/10.1189/jlb.3a0616-267r
Publication status	Published - May 2017

Keywords

Adult
CD8-Positive T-Lymphocytes/drug effects
Cell Count
Cohort Studies
Cotinine/blood
Dendritic Cells/drug effects
Dipeptidyl Peptidase 4/genetics
Female
Gene Expression Regulation/immunology
Granulocytes/drug effects
Humans
Immunophenotyping
Inducible T-Cell Co-Stimulator Ligand/genetics
Male
Middle Aged
Monocytes/drug effects
Multiple Sclerosis/etiology
NK Cell Lectin-Like Receptor Subfamily B/genetics
Primary Cell Culture
Smoking/adverse effects

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Cite this

@article{128d1c6a46284a81b0f4b6e7d9218556,

title = "Smoking reduces circulating CD26hi CD161hi MAIT cells in healthy individuals and patients with multiple sclerosis",

abstract = "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.",

keywords = "Adult, CD8-Positive T-Lymphocytes/drug effects, Cell Count, Cohort Studies, Cotinine/blood, Dendritic Cells/drug effects, Dipeptidyl Peptidase 4/genetics, Female, Gene Expression Regulation/immunology, Granulocytes/drug effects, Humans, Immunophenotyping, Inducible T-Cell Co-Stimulator Ligand/genetics, Male, Middle Aged, Monocytes/drug effects, Multiple Sclerosis/etiology, NK Cell Lectin-Like Receptor Subfamily B/genetics, Primary Cell Culture, Smoking/adverse effects",

author = "Cecilie Ammitzb{\o}ll and Lars B{\"o}rnsen and {Romme Christensen}, Jeppe and Rikke Ratzer and {Romme Nielsen}, Birgitte and S{\o}ndergaard, {Helle B} and {von Essen}, {Marina R} and Finn Sellebjerg",

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year = "2017",

month = may,

doi = "10.1189/jlb.3a0616-267r",

language = "English",

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pages = "1211--1220",

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publisher = "Federation of American Societies for Experimental Biology",

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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 -