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*Section of Oral Biology, College of Dentistry,
Department of Molecular Virology, Immunology and Medical Genetics,
Institute for Behavioral Medicine Research, College of Medicine, and
¶Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210;
The Pennsylvania State University College of Medicine, Hershey, PA 17033; and
||Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599
Immunological memory (MEM) development is affected by stress-induced neuroendocrine mediators. Current knowledge about how a behavioral interaction, such as social defeat, alters the development of adaptive immunity, and MEM is incomplete. In this study, the experience of social disruption stress (SDR) prior to a primary influenza viral infection enhanced the frequency and function of the T cell memory pool. Socially stressed mice had a significantly enlarged population of CD8+ T cells specific for the immunodominant NP366–74 epitope of A/PR/8/34 virus in lung and spleen tissues at 6–12 wk after primary infection (resting memory). Moreover, during resting memory, SDR-MEM mice responded with an enhanced footpad delayed-type hypersensitivity response, and more IFN-
–producing CD4+ T cells were detected after ex vivo stimulation. When mice were rechallenged with A/PR/8/34 virus, SDR-MEM mice terminated viral gene expression significantly earlier than MEM mice and generated a greater DbNP366–74CD8+ T cell response in the lung parenchyma and airways. This enhancement was specific to the T cell response. SDR-MEM mice had significantly attenuated anti-influenza IgG titers during resting memory. Similar experiments in which mice were primed with X-31 influenza and challenged with A/PR/8/34 virus elicited similar enhancements in the splenic and lung airway DbNP366–74CD8+ T cell populations in SDR-MEM mice. This study demonstrates that the experience of repeated social defeat prior to a primary viral infection significantly enhances virus-specific memory via augmentation of memory T cell populations and suggests that social stressors should be carefully considered in the design and analysis of future studies on antiviral immunity.
Address correspondence and reprint requests to Dr. John F. Sheridan, Section of Oral Biology, College of Dentistry, The Ohio State University, P.O. Box 182357, Columbus, OH 43218. E-mail address: sheridan.1{at}osu.edu
This work was supported by grants from the National Institute of Mental Health (RO1 MH46801-17) and the National Institute of Dental and Craniofacial Research (T32DE014320-08 to J.F.S. and F30 DE17068-03 to J.W.M).
The online version of the article contains supplemental material.
Abbreviations used in this paper:
BAL, bronchoalveolar lavage; CI, confidence interval; CT, cycle threshold; DC, dendritic cell; DCT, delta CT; DTH, delayed-type hypersensitivity; GC, glucocorticoid; GMT, geometric mean titer; HAU, hemagglutinating unit; HPA, hypothalamic-pituitary-adrenal; MEM, immunological memory; MFI, mean fluorescence intensity; MLN, mediastinal lymph node; RM-ANOVA, repeated-measures–ANOVA; SDR, social disruption stress; UV-PR8, UV-inactivated A/PR/8/34 virus.
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