THE IMPACT OF PSYCHOLOGICAL STRESS ON THE EFFICACY OF ANTIVIRAL ADOPTIVE IMMUNOTHERAPY IN AN IMMUNOCOMPROMISED HOST

Adoptive immunotherapy represents a potentially effective approach by which to control the extent of viral infections in an immunocompromise d host. However, the impact of psychological stress and its associated neuroendocrine components on the efficacy of such a treatment strateg y has yet to be determined. In the studies described herein, we have d eveloped and utilized a model of primary, local herpes simplex virus ( HSV) infection in radiation-induced, immunosuppressed C57BL/6 mice to investigate the role of stress in altering the protective capacity of adoptively transferred lymphocytes that contribute to the resolution o f primary HSV infection. The sublethal dose of irradiation chosen for this model was shown to abrogate the local, adaptive immune response t o HSV infection as measured by the degree of in vivo lymphoproliferati on, development of HSV-specific cytotoxic T lymphocytes (CTL), and pro duction of gamma interferon (IFN-gamma). Both short-and long-term acut e stress, applied in the form of physical restraint, diminished the ef fectiveness of adoptively transferred lymphocytes as was indicated by an enhancement of viral replication in the footpad tissue and an incre ased rate of mortality. A reduction in the levels of IFN-gamma at the site of primary HSV infection represented at least one mechanism under lying this suppression of anti-viral immunity. Furthermore, the time-d ependent restoration of immune function following irradiation was show n to be compromised in mice subjected to the restraint stress procedur e. Together, these findings emphasize the potential role of psychologi cal stress in suppressing both the capability of adoptive immunotherap eutic procedures to combat viral infection and the reestablishment of immune function in individuals who have undergone immunosuppressive th erapy.