Influenza virus-specific immunological memory is enhanced by repeated social defeat.
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-gamma-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 D(b)NP(366-74)CD8(+) 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 D(b)NP(366-74)CD8(+) 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.
Mays
Jacqueline W
JW
Section of Oral Biology, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA.
Bailey
Michael T
MT
Hunzeker
John T
JT
Powell
Nicole D
ND
Papenfuss
Tracey
T
Karlsson
Erik A
EA
Padgett
David A
DA
Sheridan
John F
JF
D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D001522:Behavior, Animal; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000523:psychology; D007156:Immunologic Memory; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000523:psychology; D013315:Stress, Psychological / Q000276:immunology* / Q000821:virology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte