Analysis of CD8+ T cell-mediated anti-viral responses in mice with targeted deletions of the M1 or M5 muscarinic cholinergic receptors

A number of studies have demonstrated that non-neuronal acetylcholine can play a role in the regulation of T cell function. Recently, we reported that CD8+ T cells, from mice with a targeted deletion of the M1 muscarinic receptor, had a defect in differentiating into cytolytic T lymphocytes when stimulated in vitro. In the current report, we analyze the in vivo function of CD8+ T cells from mice with targeted deletions of either M1 or M5 muscarinic receptors. M1 or M5 knockout mice were infected with either lymphocytic choriomeningitis virus or vesicular stomatitis virus. Expansion of anti-viral CD8+ T cells was monitored by staining with tetramer reagents specific for the immunodominant peptides of the viruses. No defect in expansion of CD8+ T cells was observed in either M1 or M5 knockout mice. The extent to which one can draw a generalized conclusion that M1 and M5 are not involved in anti-viral immunity depends upon issues of antigen strength, genetic background, induction of redundant receptors, and the potential for qualitative defects in the expanded CD8+ T cells.