The impact of psychological stress on the efficacy of anti-viral adoptive immunotherapy in an immunocompromised host.
Adoptive immunotherapy represents a potentially effective approach by which to control the extent of viral infections in an immunocompromised host. However, the impact of psychological stress and its associated neuroendocrine components on the efficacy of such a treatment strategy has yet to be determined. In the studies described herein, we have developed 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 of primary HSV infection. The sublethal dose of irradiation chosen for this model was shown to abrogate the local, adaptive immune response to HSV infection as measured by the degree of in vivo lymphoproliferation, development of HSV-specific cytotoxic T lymphocytes (CTL), and production of gamma interferon (IFN-gamma). Both short- and long-term acute stress, applied in the form of physical restraint, diminished the effectiveness of adoptively transferred lymphocytes as was indicated by an enhancement of viral replication in the footpad tissue and an increased rate of mortality. A reduction in the levels of IFN-gamma at the site of primary HSV infection represented at least one mechanism underlying this suppression of anti-viral immunity. Furthermore, the time-dependent restoration of immune function following irradiation was shown to be compromised in mice subjected to the restraint stress procedure. Together, these findings emphasize the potential role of psychological stress in suppressing both the capability of adoptive immunotherapeutic procedures to combat viral infection and the reestablishment of immune function in individuals who have undergone immunosuppressive therapy.
Bonneau
R H
RH
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey 17033, USA. rbonneau@bcmic.hmc.psu.edu
Brehm
M A
MA
Kern
A M
AM
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000528:radiation effects; D000918:Antibody Specificity; D005528:Foot; D006561:Herpes Simplex / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016867:Immunocompromised Host / Q000276:immunology*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology / Q000503:physiopathology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012149:Restraint, Physical; D018139:Simplexvirus / Q000276:immunology*; D013315:Stress, Psychological / Q000276:immunology*; D013997:Time Factors; D014916:Whole-Body Irradiation
D007371:Interferon-gamma