Tissue-resident NK cells do their own glandscaping.

In this issue of JEM, Sparano et al. (https://doi.org/10.

NK cells restrain cytotoxic CD8 T cells in the submandibular gland via PD-1-PD-L1.

The increasing use of anti-programmed cell death 1 (PD-1) immune checkpoint blockade has led to the emergence of immune-related adverse events (irAEs), including dysfunction of the submandibular gland (SMG). In this study, we investigated the immunoregulatory mechanism contributing to the susceptibility of the SMG to irAEs. We found that the SMGs of PD-1-deficient mice and anti-programmed cell death ligand 1 (PD-L1)-treated mice harbor an expanded population of CD8 T cells.

PD-1 Mediated Regulation of Unique Activated CD8 T Cells by NK Cells in the Submandibular Gland.

Unlabelled: The increasing utilization of anti-PD-1 immune checkpoint blockade (ICB) has led to the emergence of immune-related adverse events (irAEs), including sicca syndrome. Interestingly, we found that the submandibular gland (SMG) of PD-1 deficient mice harbors a large population of CD8 T cells, reminiscing ICB induced sicca. This phenotype was also observed in the SMG of both NK cell-depleted C57BL/6 animals and NK cell-deficient animals.

The Invariant NKT Cell Response Has Differential Signaling Requirements during Antigen-Dependent and Antigen-Independent Activation.

Invariant NKT (iNKT) cells are an innate-like population characterized by their recognition of glycolipid Ags and rapid cytokine production upon activation. Unlike conventional T cells, which require TCR ligation, iNKT cells can also be stimulated independently of their TCR. This feature allows iNKT cells to respond even in the absence of glycolipid Ags, for example, during viral infections.