Nicotine Inhibits Memory CTL Programming

Abstract

Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development.

Expression and Functional Role of α7 Nicotinic Receptor in Human Cytokine-stimulated Natural Killer (NK) Cells

“…Such a difference in ␣7 nAChR expression between these two species has also been shown in lymphocytes (8,30,32,39,40), and may underlie a different neuroimmunomodulatory potential of lymphoid cells in them. In mouse, nicotine exposure impairs the ability of NK cells to kill target cells and release cytokines through ␤2-containing nAChRs (29).…”

IL-12 stimulates CTLs to secrete exosomes capable of activating bystander CD8+ T cells

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