Effects of cigarette smoke on the immune system

Sopori, Mohan L.

doi:10.1038/nri803

Cited by 1,066 publications

(972 citation statements)

References 57 publications

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“…This may be required to synchronize and balance ionic and metabolic events in a single lymphocyte. The fact that activation of CD4 and CD8 cells through TCR/CD3 cross-linking produced distinct changes in the nAChR and mAChR repertoires, taking together with previous reports that nicotinic and muscarinic stimulations of T cells alter their TCR-dependent activities, 47,48 and that CD3z and a7 nAChR can be co-immunoprecipitated, 49 suggests strongly that ACh signaling is essential for T-cell activation. Hence, alterations within the T-cell ACh regulatory axis may provide for a fine tuning of the T cells to changing environment.…”

Section: Cholinergic Receptors Of Murine T Cells J Qian Et Alsupporting

confidence: 56%

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

et al. 2011

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Acetylcholine (ACh) regulates vital functions of T cells by acting on the nicotinic and muscarinic classes of cholinergic receptors, nAChR and mAChRs, respectively. This study was performed in murine splenic T cells. In freshly isolated CD4 and CD8 T cells, we detected mRNAs encoding a5, a9, a10, b1, b2, b4 nAChR subunits and M 1 , M 3 , M 4 and M 5 mAChR subtypes, whereas a2 was detected only in CD8 T cells. In vitro activation of CD4 T cells through T-cell receptor (TCR)/CD3 cross-linking was associated with the appearance of a4 and a7, upregulation of a5, a10, b4, M 1 and M 5 and downregulation of a9 and b2, whereas in vitro activation of CD8 T cells also featured the appearance of a4 and a7, as well as upregulation of a2, a5, b4, M 1 and M 4 , and downregulation of a10, b1, b2 and M 3 . In vitro polarization toward T helper (Th) 1 lineage was associated with a decrease of b2, b4 and M 3 expression; that toward Th2 cells with downregulation of a9 and M 3 , and upregulation of M 1 and M 5 ; and that toward Th17 phenotype with downregulation of a9, a10, b2 and M 3 mAChR. Polarized T cells also expressed a4, but not a1, a2, a3, a6, b3 or M 2 . To determine the role of cholinergic receptors in mediating the immunoregulatory action of autocrine/paracrine ACh, we analyzed the effects of nicotinic and muscarinic agonists ± antagonists on cytokine production in the CD4 þ CD62L þ T cells co-stimulated via TCR/CD3 cross-linking. The nicotinergic stimulation upregulated interferon-g (IFN-g) and downregulated interleukin (IL)-17 secretion, whereas the muscarinic stimulation enhanced IL-10 and IL-17 and inhibited INF-g secretion. These results demonstrated plasticity of the T-cell cholinergic system.

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Section: Cholinergic Receptors Of Murine T Cells J Qian Et Alsupporting

confidence: 56%

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

et al. 2011

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“…AhR activation by TCDD causes profound suppression of immune responses to a variety of Ags, and epidemiological data show that exposure to dioxins, polychlorinated biphenyls, and PAHs correlates with diminished vaccine efficacy and an increased incidence of influenza and other respiratory infections (27)(28)(29), suggesting that environmental exposure to AhR agonists affects antiviral immunity. However, the underlying mechanism for AhR-mediated immune suppression is not entirely clear.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, T cell-dependent responses and host resistance to infection are extremely sensitive targets for modulation by AhR agonists (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Although the molecular mechanisms that underlie these effects are not entirely clear, epidemiological data suggest that exposure to pollutants that contain AhR agonists correlates with diminished host resistance, altered immune function, and an increased incidence of influenza and other respiratory infections (27)(28)(29), suggesting a possible cause and effect relationship between exposure to AhR ligands and altered host resistance to infection.…”

mentioning

confidence: 99%

Aryl Hydrocarbon Receptor Activation Impairs the Priming but Not the Recall of Influenza Virus-Specific CD8+ T Cells in the Lung

Lawrence

Roberts

Neumiller

et al. 2006

The Journal of Immunology

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The response of CD8+ T cells to influenza virus is very sensitive to modulation by aryl hydrocarbon receptor (AhR) agonists; however, the mechanism underlying AhR-mediated alterations in CD8+ T cell function remains unclear. Moreover, very little is known regarding how AhR activation affects anamnestic CD8+ T cell responses. In this study, we analyzed how AhR activation by the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the in vivo distribution and frequency of CD8+ T cells specific for three different influenza A virus epitopes during and after the resolution of a primary infection. We then determined the effects of TCDD on the expansion of virus-specific memory CD8+ T cells during recall challenge. Adoptive transfer of AhR-null CD8+ T cells into congenic AhR+/+ recipients, and the generation of CD45.2AhR−/−→CD45.1AhR+/+ chimeric mice demonstrate that AhR-regulated events within hemopoietic cells, but not directly within CD8+ T cells, underlie suppressed expansion of virus-specific CD8+ T cells during primary infection. Using a dual-adoptive transfer approach, we directly compared the responsiveness of virus-specific memory CD8+ T cells created in the presence or absence of TCDD, which revealed that despite profound suppression of the primary response to influenza virus, the recall response of virus-specific CD8+ T cells that form in the presence of TCDD is only mildly impaired. Thus, the delayed kinetics of the recall response in TCDD-treated mice reflects the fact that there are fewer memory cells at the time of reinfection rather than an inherent defect in the responsive capacity of virus-specific memory CD8+ cells.

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“…Nicotine is the main immunosuppressive constituent of cigarette smoke, which inhibits both the innate and adaptive immune responses [27]. Smoking may have an 'antioestrogenic' effect although endogenous oestrogen levels have not been found to differ significantly when comparing current smokers with former smokers or non-smokers [28].…”

Section: Biological Mechanismmentioning

confidence: 99%