NK cells share a universal signature of memory with B and T cells in mice and humans 3891

Abstract Description NK cells, like B and T cells, acquire immune memory; however, our understanding of memory NK cells is primarily limited to specific subsets generated during CMV infection and lacks generalized memory markers. We hypothesized a universal memory signature exists across B, T, and NK cells; thus, we performed whole transcriptional profiling of B, CD4 T, CD8 T, and NK cells over the course of MCMV infection. Indeed, a shared transcriptional signature delineated naïve and memory cells across all lymphocyte populations; including CD55 (DAF, decay accelerating factor), the ectonucleotidase CD39, and the transcription factor Aiolos which were all validated by flow cytometry. As such, naïve cells are CD55hiCD39-Aioloshi and memory are any other combination thereof. The capacity of these markers to delineate memory cells extended to multiple other infectious scenarios and were recapitulated in human memory B and T cells. Single cell transcriptional analysis of human lymphocytes also demonstrated functional distinction between naïve and memory cells. To solidify this memory signature for NK cells, we performed in vitro stimulation and observed upregulation of cytolytic effectors only in memory NK cells. Notably, naïve and memory NK cells exhibit distinct localization throughout the human body. These findings establish a core signature, conserved across cell lineage and species, for identifying memory broadly and provides a foundation for designing strategies to modulate immune memory. Funding Sources NIH AI168634, AI128949, T32AI148099 Topic Categories Viral Immunology (VIR)