HVEM Imprints Memory Potential on Effector CD8 T Cells Required for Protective Mucosal Immunity

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Mucosal immunity is vital for protection against reinfection by virulent viruses.
• Memory CD8 T cells are essential for sustained mucosal immunity and reside at the site of initial infection.
• Memory precursor effector cells (MPECs) are distinct from short-lived effector cells and are precursors to memory T cells.

Purpose of the Study:

• To investigate the role of herpes virus entry mediator (HVEM) in the persistence of memory CD8 T cells at mucosal sites.
• To determine if HVEM signaling is critical for the development of protective memory CD8 T cell populations.

Main Methods:

• Utilized a respiratory virus infection model in mice.
• Generated and analyzed herpes virus entry mediator (HVEM)-deficient CD8 T cells.
• Performed adoptive transfer experiments to assess MPEC survival and memory cell development.
• Evaluated protection against secondary influenza virus infection in HVEM-deficient recipients.

Main Results:

• HVEM-deficient CD8 T cells showed normal expansion but skewed away from MPECs.
• HVEM was selectively expressed on MPECs, and HVEM-deficient MPECs failed to survive adoptive transfer.
• HVEM deficiency resulted in poor development of circulating and lung-resident memory CD8 T cells.
• HVEM-deficient recipients were unable to mount protective immunity against reinfection with influenza virus.

Conclusions:

• Herpes virus entry mediator (HVEM) provides critical signals necessary for the persistence of memory precursor effector cells (MPECs).
• HVEM signaling is essential for the generation of protective CD8 T cell-based mucosal memory.
• Targeting HVEM may be a strategy to enhance long-term immunity against respiratory viral infections.