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.