Journal
JOURNAL OF VIROLOGY
Volume 92, Issue 16, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00495-18
Keywords
dendritic cells; CD8 T cells; vaccinia; respiratory; lung; effector functions; lung infection; poxvirus; vaccinia virus
Categories
Funding
- NIH [AI77079, AI087734, T32 AR007603-15]
- American Association of Immunologists Careers in Immunology Fellowship Program
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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 CD8 alpha(+) 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-gamma)-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. IMPORTANCE During respiratory infection with vaccinia virus (VacV), a member of Poxviridae 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-gamma 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.
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