G-Protein Coupled Receptor 18 Contributes to Establishment of the CD8 Effector T Cell Compartment

The requirements for effector and memory CD8 T cell development are incompletely understood. Recent work has revealed a role for G-protein coupled receptor 18 (GPR18) in establishment of the intestinal CD8αα intraepithelial lymphocyte compartment. Here, we report that GPR18 is also functionally expressed in conventional CD8αβ T cells. When the receptor is lacking, mice develop fewer CD8⁺ KLRG1⁺ Granzyme B⁺ effector-memory cells. Bone marrow chimera studies show that the GPR18 requirement is CD8 T cell intrinsic. GPR18 is not required for T-bet expression in KLRG1⁺ CD8 T cells. Gene transduction experiments confirm the functional activity of GPR18 in CD8 T cells. In summary, we describe a novel GPCR requirement for establishment or maintenance of the CD8 KLRG1⁺ effector-memory T cell compartment. These findings have implications for methods to augment CD8 effector cell numbers.