Key Points Clonal-like expansion of NK cells in response to CMV infection causes stable imprints in the human KIR repertoire. Education by inhibitory KIRs promotes the expansion of NK cells, causing repertoire skewing and a bias for self-specific inhibitory KIRs.

SummaryInfection by human cytomegalovirus (HCMV) leads to NKG2C-driven expansion of adaptive natural killer (NK) cells, contributing to host defense. However, approximately 4% of all humans carry a homozygous deletion of the gene that encodes NKG2C (NKG2C−/−). Assessment of NK cell repertoires in 60 NKG2C−/− donors revealed a broad range of NK cell populations displaying characteristic footprints of adaptive NK cells, including a terminally differentiated phenotype, functional reprogramming, and epigenetic remodeling of the interferon (IFN)-γ promoter. We found that both NKG2C− and NKG2C+ adaptive NK cells expressed high levels of CD2, which synergistically enhanced ERK and S6RP phosphorylation following CD16 ligation. Notably, CD2 co-stimulation was critical for the ability of adaptive NK cells to respond to antibody-coated target cells. These results reveal an unexpected redundancy in the human NK cell response to HCMV and suggest that CD2 provides “signal 2” in antibody-driven adaptive NK cell responses.

Experimental design: Sixteen patients received fludarabine/cyclophosphamide conditioning 68 combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-69 activated haploidentical NK cells. 70

Ethnic racial socialization (ERS) processes include cultural socialization (enculturation), preparation for bias, and promotion of mistrust. Although often conflated, these processes may variably confer psychological risk or protection. Cultural socialization has often been found to be protective, whereas promotion of mistrust has at times been associated with risk. We hypothesized that the distinctive associations between ERS processes and depression might be explained by trait optimism and pessimism as potential mediators. Results from a sample of 670 African American, Latino, and Asian American young adults indicated that cultural socialization was negatively associated with depression, whereas preparation for bias and promotion of mistrust were positively associated with depression. Participants who reported that their families engaged in cultural socialization had a more optimistic and less pessimistic outlook, which in turn explained lower levels of depression symptoms. In contrast, reported familial preparation for bias and promotion of mistrust were linked to greater pessimism and less optimism, which in turn were associated with depression symptoms. Although there were racial/ethnic differences in mean levels of ERS processes, multigroup analyses revealed that the associations with depression symptoms were robust across groups.