Choline Acetyltransferase-Expressing T cells are rare in young mice

Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor on macrophages. Nerve fibers in spleen lack the machinery necessary for acetylcholine production. Instead, an acetylcholine-producing, memory phenotype T cell relays the neural signal. These choline acetyltransferase+ (ChAT+) T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the acetylcholine required to control innate immune responses. The understanding of the phenotype of ChAT+ T cells is incomplete. Using flow cytometry, we detected TCRβ+ but no TCRγδ+ ChAT+ T cells. Since acetylcholine-producing T cells are memory cells, we hypothesized that this relay function is acquired, and investigated the splenic ChAT+ T cell population early in life. Indeed, splenic ChAT+ T cells were rare in 2 to 25 days old mice (2%±0.3 of ChAT+ cells) while B cells constituted the majority of the ChAT+ splenocytes (86±5%). In contrast, frequencies of ChAT+ T cells varied considerably in adults and could constitute 1/4 of the ChAT+ population. The infrequency of ChAT+ T cells early in life suggests that the inflammatory reflex may be impaired in young mice.