Acetylcholine released from T cells regulates intracellular Ca2+, IL-2 secretion and T cell proliferation through nicotinic acetylcholine receptor

• Published in: Life sciences (1973) 2017-03, Vol.172, p.13-18
• Main Authors: Mashimo, Masato, Iwasaki, Yukari, Inoue, Shoko, Saito, Shoko, Kawashima, Koichiro, Fujii, Takeshi
• Format: Article
• Language: English
• Subjects: Acetylcholine; Interleukin-2; Nicotinic acetylcholine receptor; Spontaneous [Ca2 +]i increase; T cells
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2016.12.015

T lymphocytes synthesize acetylcholine (ACh) and express muscarinic and nicotinic ACh receptors (mAChR and nAChR, respectively) responsible for increases in the intracellular Ca2+ concentration ([Ca2+]i). Our aim in the present study was to assess whether autocrine ACh released from T lymphocytes regulates their physiological functions. MOLT-3 human leukemic cell line and murine splenocytes were loaded with fura-2 to monitor [Ca2+]i changes in the absence or presence of several AChR antagonists, including mecamylamine, methyllycaconitine and scopolamine. Real-time PCR and ELISA were performed to measure interleukin-2 (IL-2) mRNA and protein levels. T lymphocytes constitutively produce sufficient amounts of ACh to elicit autocrine changes in [Ca2+]i. These autocrine ACh-evoked [Ca2+]i transients were mediated by nAChRs and then influx of extracellular Ca2+. Mecamylamine, a nAChR inhibitor, suppressed not only these [Ca2+]i transients, but also IL-2 release and T cell proliferation. Here, we confirmed that T lymphocytes utilize ACh as a tool to interact with each other and that autocrine ACh-activated nAChRs are involved in cytokine release and cell proliferation. These findings suggest the possibility that nAChR agonists and antagonists and smoking are able to modulate immune function, which in turn suggests the therapeutic potential of immune activation or suppression using nAChR agonists or antagonists.