T cells are thought to be important for control of SARS-CoV-2 infection, but little is known about the host factors that promote T cell responses in the respiratory tract. We used non-human primates to investigate the regulation of respiratory immunity during mild SARS-CoV-2 infection. We first examined the kinetics of viral replication, inflammation, and host immune responses. Foci of inflammation detected with 18FDG-PET/CT imaging peaked within 2-3 days of infection. Single cell RNA sequencing revealed an early influx of IFN-activated myeloid cells into the airways, which correlated with viral RNA loads. Antigen-specific T cell responses were first detected after inflammation and viral replication had resolved and were preferentially localized to the lower airways. We next examined the role of pro and anti-inflammatory cytokines, IFNγ and IL-10, on immunity to SARS-CoV-2 infection by blocking these cytokines with monoclonal antibodies early during infection. IFNγ blockade decreased lung inflammation but had no major impact on adaptive immune responses. In contrast, IL-10 blockade increased lung inflammation and enhanced accumulation of virus-specific T cells in the lower airways. IL-10 blockade also inhibited the differentiation of virus-specific T cells into airway CD69+CD103+ tissue resident memory cells (TRM). While virus-specific T cells were undetectable in the nasal mucosa, IL-10 blockade similarly reduced the frequency of bystander TRM cells in the nasal mucosa. Thus, in the setting of mild SARS-COV-2 infection IL-10 has a key role in suppressing local lung inflammation and the accumulation of SARS-CoV-2-specific T cells, while also promoting TRM at respiratory mucosal surfaces.
