Increase of Inhibitory Siglec receptors on T cells mitigates severe immune reactions during acute viral infections

Expression of inhibitory Siglec receptors has been described on T cells of patients with viral infection and cancer. However, the exact function and their role in T-cell activation and control of infections have not been well investigated. Here, we show that Siglec-9 levels increase on T cells in patients with acute severe acute respiratory syndrome coronavirus 2 infection relative to levels on healthy controls. T cells of these patients are inhibited by Siglec-9, and specific blocking with antibodies released this inhibition. To further test the role of Siglec-9 in acute viral infections, we characterized a murine model with T-cell intrinsic Siglec-9 overexpression. We found that Siglec-9 restricted T-cell immunity after acute infection with lymphocytic choriomeningitis virus, thereby dampening T-cell-mediated immune pathology. These results show that inhibitory Siglec receptors including Siglec-9 T cell intrinsically modulate and fine-tune antiviral T-cell activation, proliferation, and effector function.