CD8+ T Cells Promote Maturation of Liver-Resident NK Cells Through the CD70-CD27 axis

Abstract

Liver-resident natural killer (LrNK) cells are a unique subset of NK cells that are distinct from conventional NK cells. However, little is known about the mechanisms by which LrNK cells mature. In this study, we discovered that LrNK cells exhibit a relatively immature phenotype and impaired cytotoxic capacity in the absence of CD8⁺ T cells. The provision of CD8⁺ T cells to Cd8^-/- or Rag1^-/- mice led to the restoration of LrNK cell maturation. Furthermore, co-culture with CD8⁺ T cells induced immature CD27⁺ LrNK cells to convert into mature CD27^- LrNK cells, whereas blocking the interaction of CD70 and CD27 abrogated the ability of CD8⁺ T cells to promote the maturation of LrNK cells. Conclusion: Our findings indicate that CD8⁺ T cells promote the maturation of LrNK cells through the CD70-CD27 axis, and therefore highlight a previously unknown mechanism responsible for the mediation of LrNK cell maturation.