Cowpox immunomodulation of a pulmonary immune response to OVA‐peptide

Abstract

Cowpox virus (CPXV), a close relative of the deadly variola virus causing smallpox, is primarily a lung pathogen and is known to transmit through aerosols. Prior work in our lab suggests that CPXV suppresses dendritic cell function in vitro and leaves them unable to stimulate T cells. We have developed an in vivo murine model system to directly assess the impact of an ongoing pulmonary CPXV infection on the response to a second antigen entering the lungs (OVA323‐339 peptide). Using adoptively transferred DO11.10 T cells that respond to OVA peptide, we have shown that a lethal CPXV infection reduces DO11.10 T cell proliferation in the lung‐associated lymph node (LALN), while proliferation can still occur during a sublethal infection. DCs in the LALN of CPXV infected mice have decreased expression of co‐stimulatory molecules CD80 and CD86 as well as CD1d, a lipid antigen presentation molecule. The number of infected DCs may account for the difference seen in sublethal and lethal infections. Using recombinant CPXV expressing enhanced green fluorescent protein, we determined that 32% of lung DCs are infected at the lethal dose of virus (day 6 post‐infection), while only 6% of DCs are infected at the sublethal dose. This may explain the difference in DO11.10 T cell proliferation using the two doses of virus, and the importance of functioning DCs in the lung to prevent against secondary infection in the pulmonary CPXV model.