Tissue-specific determinants of the adaptive NK cell response

Abstract Natural killer (NK) cells are circulating innate lymphocytes that poised to respond rapidly upon encounter with cancer or virally-infected as well proinflammatory cytokines. In addition their early role in immune responses, it is now appreciated NK can also take on features of adaptive such antigen-specific clonal expansion and long-lived memory these processes best characterized following cytomegalovirus (CMV) infection mouse human. cell receptor recognition virally-encoded proteins drives CMV-specific cells, but the signals collectively give rise still not fully understood. Mouse (MCMV) systemic while exhibit cytokine-induced activation across multiple tissue sites infection, we were surprised find MCMV-specific occurs predominantly spleen. Transcriptional analysis indicated canonical non-canonical NF-kb components may be engaged a greater extent primed spleen, further identified TNFa signaling critical regulator both responses through engagement distinct downstream arms. Notably, TNFR2-deficient exhibited hyper-activation ultimately failed undergo strong proliferative burst observed These findings highlight central spleen facilitating innate-to-adaptive transition provide insight into how better generate immunity diverse settings. Adriana M. Mujal supported by Cancer Research Institute Institute/Amgen Fellow.