TY - JOUR
T1 - The dual role of CD8+ T lymphocytes in the development of stress-induced herpes simplex encephalitis
AU - Anglen, Crystal S.
AU - Truckenmiller, M. E.
AU - Schell, Todd D.
AU - Bonneau, Robert H.
N1 - Funding Information:
We thank Dr. Satvir Tevethia for the recombinant vaccinia virus, rVVESgB498–505, and the gB498–505/class I H-2K b tetramer. We also thank Melanie Epler for technical assistance in preparing the gB498–505/class I H-2K b tetramer. Special thanks to Jodi Yorty, Aji Nair, and Heidi Young for their helpful discussions. This work was supported by Public Health Research Grant AI49719 from the National Institutes of Health.
PY - 2003/7
Y1 - 2003/7
N2 - Despite the generally restrictive nature of the blood-brain barrier (BBB), circulating lymphocytes can infiltrate into the central nervous system (CNS) during a variety of disease states. Although the contributions of these lymphocytes to CNS-associated disease have been identified in some viral models, the factors which govern this infiltration following herpes simplex virus (HSV) infection remain to be elucidated. We have developed a murine model of HSV encephalitis (HSE) to define the relationship among psychological stress, the recruitment of HSV-specific T cells into the CNS, and the development of HSE. Naive mice, as well as mice that had been vaccinated with a recombinant vaccinia virus (rVVESgB498-505) that elicits the generation of HSV-1 gB498-505-specific CD8+ T cells, were infected intranasally (i.n.) with HSV-1 McIntyre. Beginning one day prior to HSV-1 infection and continuing for a total of 9 days, naive and vaccinated mice were exposed to a well-established stressor, restraint stress. Naive, stressed mice exhibited increased symptoms of HSE and HSE-associated mortality as compared to non-stressed controls. A concomitant increase in CD4+ and CD8+ T cells in the brain was observed throughout the infection, with CD8+ T cells outnumbering CD4+ T cells. The development of HSE in these naive, stressed mice was accompanied by a delayed infiltration of gB498-505-specific CD8+ T cells after HSV spread into the brain. In contrast, both stressed and non-stressed rVVESgB498-505-vaccinated mice possessed gB498-505-specific CD8+ T cells prior to HSV challenge and were protected against HSE despite having detectable HSV-1 DNA in the brain. Together, these findings suggest that a delayed infiltration of CD8+ T cells into the brain may promote HSE in naive mice, while the presence of HSV-specific CD8+ T cells in the brain prior to HSV challenge is protective, possibly by limiting HSV replication and spread within the CNS.
AB - Despite the generally restrictive nature of the blood-brain barrier (BBB), circulating lymphocytes can infiltrate into the central nervous system (CNS) during a variety of disease states. Although the contributions of these lymphocytes to CNS-associated disease have been identified in some viral models, the factors which govern this infiltration following herpes simplex virus (HSV) infection remain to be elucidated. We have developed a murine model of HSV encephalitis (HSE) to define the relationship among psychological stress, the recruitment of HSV-specific T cells into the CNS, and the development of HSE. Naive mice, as well as mice that had been vaccinated with a recombinant vaccinia virus (rVVESgB498-505) that elicits the generation of HSV-1 gB498-505-specific CD8+ T cells, were infected intranasally (i.n.) with HSV-1 McIntyre. Beginning one day prior to HSV-1 infection and continuing for a total of 9 days, naive and vaccinated mice were exposed to a well-established stressor, restraint stress. Naive, stressed mice exhibited increased symptoms of HSE and HSE-associated mortality as compared to non-stressed controls. A concomitant increase in CD4+ and CD8+ T cells in the brain was observed throughout the infection, with CD8+ T cells outnumbering CD4+ T cells. The development of HSE in these naive, stressed mice was accompanied by a delayed infiltration of gB498-505-specific CD8+ T cells after HSV spread into the brain. In contrast, both stressed and non-stressed rVVESgB498-505-vaccinated mice possessed gB498-505-specific CD8+ T cells prior to HSV challenge and were protected against HSE despite having detectable HSV-1 DNA in the brain. Together, these findings suggest that a delayed infiltration of CD8+ T cells into the brain may promote HSE in naive mice, while the presence of HSV-specific CD8+ T cells in the brain prior to HSV challenge is protective, possibly by limiting HSV replication and spread within the CNS.
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U2 - 10.1016/S0165-5728(03)00159-0
DO - 10.1016/S0165-5728(03)00159-0
M3 - Article
C2 - 12864968
AN - SCOPUS:0037967645
SN - 0165-5728
VL - 140
SP - 13
EP - 27
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -
