Mechanisms of Social Stress Enhancement of Virus‐specific Immune Memory

Murine studies have demonstrated that the experience of social defeat (social disruption stress, SDR) before a primary influenza virus challenge augmented memory CD8+T cell responses to viral re‐challenge. Patterning of immune memory is established by the immune response to a primary infection, and the present study was designed to investigate potential mechanisms for memory enhancement during a primary challenge. C57BL/6 mice underwent 2 hrs of SDR per night for 6 nights (SDR‐INF group), which entailed introducing an aggressive mouse that physically defeated all resident mice. After night 6 of SDR, mice were intranasally infected with 1 HAU of influenza A/PR/8. Clonal expansion was significantly enhanced in the SDR‐INF group (p<0.05) for the immunodominant DbNP366+T cell subset, but not the DbPA224+ subset. SDR‐INF mice terminated viral replication significantly earlier than INF mice, and expressed more IFNγ mRNA prior to and during A/PR/8 infection. This study suggests that social defeat‐induced enhancement of virus‐specific immune memory occurs at the activation/clonal expansion phase of a primary infection, and is mediated by both cellular and environmental factors.Supported by NIH grants F30DE17068‐02, RO1MH46801‐13, T32DE014320‐04.