IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques.

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of ¹⁸fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69⁺CD103⁺ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques. Author summary: Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 during SARS-CoV-2 infection of rhesus macaques. Whole body ¹⁸FDG-PET-CT imaging showed that IFNγ promotes SARS-CoV-2 induced pulmonary disease and IL-10 dampens the size, activity, and duration of lung lesions induced after infection. We also find a major role for IL-10 in the regulation of SARS-CoV-2-specific T cell responses. Our data show that IL-10 limits the magnitude of the effector T cell clonal burst during the acute phase of infection. We also find that following clearance of the virus, IL-10 promotes the differentiation of lung effector T cells into CD69+CD103+ tissue resident memory cells. [ABSTRACT FROM AUTHOR]