The effects of stress on memory cytotoxic T lymphocyte-mediated protection against herpes simplex virus infection at mucosal sites.

Psychological stress has been shown to affect many components of the innate and adaptive immune responses to a variety of pathogens including herpes simplex virus (HSV). Mucosal tissues are clinically relevant sites of infection with HSV as well as with many other common pathogens. However, there is a scarcity of experimental evidence that stress affects mucosal immunity. We have taken advantage of a murine model of HSV-specific immune protection that is mediated by only memory cytotoxic T lymphocytes (CTLm) specific for a single CTL recognition epitope within glycoprotein B of HSV-1 (gB498-505). This CTLm population is elicited by vaccination with a recombinant vaccinia virus, which expresses this epitope in the absence of any other HSV-encoded antigens. We report here that stress reduces the ability of gB498-505-specific CTLm to protect against a lethal intranasal or intravaginal HSV infection. Also, stress decreases the ability of these CTLm to limit virus levels at the mucosal site of infection but does not have a significant effect on the levels of virus in the innervating sensory ganglia. Finally, stress decreases protection against HSV-mediated pathology of the vaginal epithelium. These studies are the first to examine the effects of stress on CTLm activation and function in vivo.