IL-21 production by iNKT cells may be particularly critical in limiting HSV-2 replication at the site of infection as the IL-21R expression is upregulated on vaginal epithelia 1–3 days post-infection, and similar to CD1d-deficient mice, IL-21R-deficient animals have increased viral loads and higher mortality to HSV-2 (61). Here, CD1D is linked to infection.