Choline acetyltransferase+ T cells represent a discrete lymphocyte subset that regulates innate immunity. (P1008)

Abstract Neural circuits regulate cytokine production and inflammation. A vagus nerve circuit inhibits TNF production by acetylcholine signaling through the α7 nicotinic acetylcholine receptor on macrophages in spleen, but spleen nerves lack the machinery for acetylcholine biosynthesis. Instead, the nerve signal is relayed by CD4+CD44hiCD62Llow choline acetyltransferase+ (ChAT+) T cells, which produce the required acetylcholine. Understanding of the ChAT+ T cell phenotype is incomplete. mRNA levels in ChAT+ and ChAT- splenic T cells were measured by gene array. Hierarchical clustering of significantly different transcripts rendered four clusters. Expression data from the ChAT+/ChAT- dataset was also analyzed together with publicly available data on immune cell mRNA expression from the ImmGen consortium. In principal component analysis of this dataset, NK-cells, dendtritic cells/macropages, B cells and T cells formed separate clusters. ChAT+ T cells clustered among T cells, but separately from other T cell subpopulations, and were distinguished by the first principal component. Gene ontology analysis of this component showed enrichment of the G-protein coupled receptor signaling pathway, proliferation, and metabolism terms. In vitro, presence of ChAT+ T cells inhibited macrophage TNF production. Taken together, these data indicate that ChAT+ T cells are phenotypically distinct from other cell types in the ImmGen dataset and suggests that ChAT+ T cells are a novel T cell subset.