Cutting Edge: CD8+ T Cell Priming in the Absence of NK Cells Leads to Enhanced Memory Responses

Abstract

It is uncertain whether NK cells modulate T cell memory differentiation. By using a genetic model that allows the selective depletion of NK cells, we show in this study that NK cells shape CD8⁺ T cell fate by killing recently activated CD8⁺ T cells in an NKG2D- and perforin-dependent manner. In the absence of NK cells, the differentiation of CD8⁺ T cells is strongly biased toward a central memory T cell phenotype. Although, on a per-cell basis, memory CD8⁺ T cells generated in the presence or the absence of NK cells have similar functional features and recall capabilities, NK cell deletion resulted in a significantly higher number of memory Ag-specific CD8⁺ T cells, leading to more effective control of tumors carrying model Ags. The enhanced memory responses induced by the transient deletion of NK cells may provide a rational basis for the design of new vaccination strategies.