website: AADR 37th Annual Meeting

ABSTRACT: 0608  

Mechanisms of social stress enhancement of virus specific immune memory

J.W. MAYS, N.D. POWELL, T.L. PAPENFUSS, M. BAILEY, D.A. PADGETT, and J.F. SHERIDAN, Ohio State University, Columbus, USA

Objectives: Neuroendocrine mediators impact the immune system, including the mucosal immune system responsible for surveillance and protection in the upper respiratory tract.  Murine studies have demonstrated the experience of social defeat (social disruption stress, SDR) before a primary influenza virus challenge augmented immunological memory responses to viral re-challenge.  Patterning of immune memory is established by the immune response to a primary infection, during which the CD8+T cell is principally responsible for termination of viral replication.  The present study was designed to investigate potential mechanisms for memory enhancement.

Methods: Male C57BL/6 mice underwent SDR or were undisturbed (INF) before intra-nasal infection with influenza A/PR/8/34. Daily two-hour cycles entailed introduction of an aggressive mouse that defeated all resident mice. Mice were infected after the sixth (final) cycle.  Cells were isolated post-infection and assessed via flow cytometry using a peptide-specific MHC I  tetramer to identify the immunodominant NP366 response.

Results: Exposure to SDR in the absence of infection increased lung gene expression of innate cytokines IFNa and IFNb.  Following infection, SDR mice had an increased number of lung NP366-74CD8+T cells (p<0.05).  The influx originated during the clonal expansion phase, and at day 9 post-infection included more cells expressing an activated phenotype: CD25+/CD62LLO NP366-74CD8+ in SDR mice versus the INF group.  SDR mice consistently cleared influenza virus earlier from lung tissue compared to INF group.  Histologically, SDR mice had increased mononuclear cell infiltrate, consolidation and cytopathic effects in lung tissue compared to the INF group. 

Conclusions:  Social defeat, prior to primary viral infection, enhanced virus-specific CD8+T cell memory.  Enhanced memory was associated with increased expansion of antigen-specific CD8+T cells during the primary response, and with altered local factors, which may have contributed to T cell activation and earlier clearance of virus from lung tissue in SDR animals. 

Supported by NIH grants F30DE17068-02, RO1MH46801-13, T32DE014320-04.

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