Expression of human CD8+ T cells 21 d after BCL11B KO or control treatment. Expression of human CD8+ T cells 21 d after BCL11B KO or control treatment

BCL11B, an essential transcription factor for thymopoiesis, regulates also vital processes in post-thymic lymphocytes. Increased expression of BCL11B was recently correlated with the maturation of NK cells, whereas reduced BCL11B levels were observed in native and induced T cell subsets displaying NK cell features. We show that BCL11B-depleted CD8+ T cells stimulated with IL-15 acquired remarkable innate characteristics. These induced innate CD8+ (iiT8) cells expressed multiple innate receptors like NKp30, CD161, and CD16 as well as factors regulating migration and tissue homing while maintaining their T cell phenotype. The iiT8 cells effectively killed leukemic cells spontaneously and neuroblastoma spheroids in the presence of a tumor-specific monoclonal antibody mediated by CD16 receptor activation. These iiT8 cells integrate the innate natural killer cell activity with adaptive T cell longevity, promising an interesting therapeutic potential. Our study demonstrates that innate T cells, albeit of limited clinical applicability given their low frequency, can be efficiently generated from peripheral blood and applied for adoptive transfer, CAR therapy, or combined with therapeutic antibodies. Overall design: The setting included three experimental groups: non-treated control, mock electroporated control, and BCL11B knock-out. All cells were cultivated in supplemented medium. CD8+ T cells were prepared from three donors as biological replicates. Thus, nine samples were analyzed in total. Affymetrix Human Clariom S GeneChip was used for recording the global transcriptome pattern.