Pulmonary monocytes interact with effector T cells in the lung tissue to drive TRM differentiation following viral infection

Lung resident memory CD8 T cells (T-RM) are critical for protection against respiratory viruses, but the cellular interactions required for their development are poorly understood. Herein we describe the necessity of classical monocytes for the establishment of lung T-RM following influenza infection. We find that, during the initial appearance of lung T-RM, monocytes and dendritic cells are the most numerous influenza antigen-bearing APCs in the lung. Surprisingly, depletion of DCs after initial T cell priming did not impact lung T-RM development or maintenance. In contrast, a monocyte deficient pulmonary environment in CCR2-/- mice results in significantly less lung T-RM following influenza infection, despite no defect in the antiviral effector response or in the peripheral memory pool. Imaging shows direct interaction of antigen-specific T cells with antigen-bearing monocytes in the lung, and pulmonary classical monocytes from the lungs of influenza infected mice are sufficient to drive differentiation of T cells in vitro. These data describe a novel role for pulmonary monocytes in mediating lung T-RM development through direct interaction with T cells in the lung.