Batf3-Dependent Dendritic Cells Promote Optimal CD8 T Cell Responses against Respiratory Poxvirus Infection.

Respiratory infection with vaccinia virus (VacV) elicits robust CD8 T cell responses that play an important role in host resistance. In the lung, VacV encounters multiple tissue-resident antigen-presenting cell (APC) populations, but which cell plays a dominant role in priming of virus-specific CD8 effector T cell responses remains poorly defined. We used Batf3 mice to investigate the impact of CD103 and CD8α dendritic cell (DC) deficiency on anti-VacV CD8 T cell responses. We found that Batf3 mice were more susceptible to VacV infection, exhibiting profound weight loss, which correlated with impaired accumulation of gamma interferon (IFN-γ)-producing CD8 T cells in the lungs. This was largely due to defective priming since early in the response, antigen-specific CD8 T cells in the draining lymph nodes of Batf3 mice expressed significantly reduced levels of Ki67, CD25, and T-bet. These results underscore a specific role for Batf3-dependent DCs in regulating priming and expansion of effector CD8 T cells necessary for host resistance against acute respiratory VacV infection. During respiratory infection with vaccinia virus (VacV), a member of family, CD8 T cells play important role in resolving the primary infection. Effector CD8 T cells clear the virus by accumulating in the infected lungs in large numbers and secreting molecules such as IFN-γ that kill virally infected cells. However, precise cell types that regulate the generation of effector CD8 T cells in the lungs are not well defined. Dendritic cells (DCs) are a heterogeneous population of immune cells that are recognized as key initiators and regulators of T-cell-mediated immunity. In this study, we reveal that a specific subset of DCs that are dependent on the transcription factor Batf3 for their development regulate the magnitude of CD8 T cell effector responses in the lungs, thereby providing protection during pulmonary VacV infection.