Chronic spinal cord injury impairs primary CD8 T cell antiviral immunity but does not affect generation or function of memory CD8 T cells

Abstract

Antiviral immunity is severely compromised following trauma to the central nervous system. In mice with chronic spinal cord injury (SCI), primary infection with influenza virus leads to high mortality rates due to impaired expansion of virus-specific CD8 T cells. One strategy to increase resistance to viral infections is to generate memory immune cells that protect from recurrent infections. However, it is unknown if chronic SCI also impairs secondary immune responses to influenza challenge as it does primary responses. Here, we used a mouse model of chronic SCI and a clinically relevant influenza A infection to investigate CD8 T cell response. As shown previously, chronic SCI mice had impaired primary antiviral responses with high mortality rates and decreased expansion of virus-specific CD8 T cells following intranasal infection. To investigate CD8 T cell memory, we used two strains of influenza A virus [PR8(H1N1) and X31(H3N2)] that share internal proteins but differ in surface antigens. Chronic SCI mice immunized with live X31 were able to generate memory CD8 T cells that secreted IFNγ upon stimulation with viral peptides ex vivo, which was comparable to immunized uninjured mice. Importantly, immunization prior to challenge with a lethal dose of PR8 resulted in no mortality and significant CD8 T cell recall responses in both uninjured and chronic SCI mice. In addition, memory CD8 T cells generated before SCI remained functional up to 8 weeks after injury. These pre-existing memory CD8 T cells provided full protection from lethal PR8 challenge given at the chronic timepoint following injury. Overall, this study shows that memory CD8 T cells generated either before or after chronic SCI still remain functional. These results highlight the need for proper immunization of SCI patients and show the potential of memory T cells to confer protection against not only influenza, but other viral infections as well.