Pulmonary Orthopoxvirus infection compromises a murine OVA peptide immune response in a dose-dependent manner (39.8)

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Abstract Cowpox virus (CPXV), a close relative of variola virus that causes smallpox, can suppress the immune system through a large array of immunosuppressive gene products. We developed a murine model in which DO11.10 T cells specific for an OVA peptide were transferred into BALB/c mice to assess the impact of a pulmonary CPXV infection on DO11.10 T cell proliferation in lung draining lymph nodes following intranasal OVA peptide delivery. High and low-dose CPXV infections were compared. Both doses lead to clinical illness, but the high dose is lethal. A high-dose infection reduced DO11.10 T cell proliferation, but a low-dose infection did not. At the time that proliferation of T cells was assessed (6d),15±1% of lung dendritic cells (DCs) were infected at the high-dose, but only 5±1% of DCs at the low-dose. At both doses, infected and uninfected DCs had decreased expression of co-stimulatory molecules. We speculated that the lung microenvironment created by infection, rather than direct infection of the DCs, suppressed DC immune function. In support, we found that bronchoalveolar lavage fluid and supernatant derived from lung homogenates from infected mice suppressed the function of uninfected lung DCs in vitro. Furthermore, the suppressive activity was more highly concentrated in lungs from high-dose infected mice. These studies strongly suggest that orthopoxvirus infections create an immunosuppressive microenvironment that compromises the host pulmonary immune responses.