Tissue resident memory CD8 T cells limit respiratory virus transmission by IFN-γ production and activation of nasal cavity epithelial cells

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B130
Abstract ID: 4685

Presenting Author:
Sarah E. Michalets , Graduate Student at Emory Univ. Sch. of Med.

Abstract:

Many vaccines against respiratory viruses have proven suboptimal in generating long-lasting sterilizing immunity and preventing transmission among populations. It is well established that respiratory tract resident memory CD8 T cells (TRM) induced by vaccination can reduce viral burdens and limit immunopathology upon direct inoculation of respiratory viruses. However, the ability of respiratory tract CD8 TRM to limit viral transmission has remained elusive. We developed a murine model to investigate the role of respiratory tract CD8 TRM in viral transmission using Sendai virus, which naturally transmits among mice. Contact mice were first immunized to generate Sendai virus-specific CD8 TRM and challenged by co-housing with a Sendai virus-infected index mouse. We demonstrated that CD8 TRM can limit viral transmission and decrease viral burdens, even in the absence of B cell responses, CD4 T cells, and circulating effector memory T cells. We evaluated multiple CD8 T cell effector mechanisms for their importance in limiting viral transmission and determined that IFN-γ secretion was critical. Upon IFN-γ signaling, nasal cavity epithelial cells adopted an anti-viral program. Furthermore, CD8 TRM in the nasal cavity alone were sufficient to limit respiratory virus transmission. These findings suggest that respiratory tract CD8 TRM, particularly those within the upper respiratory tract, are a promising vaccine target to prevent respiratory virus transmission among populations.