Characterization of the Two Populations of NK-Like CD56+ T Cells and KIR+ T Cells in Human

Abstract 3292 Previous studies have demonstrated that many T cell subsets possess NK-like features, including the CD56 + and KIR + populations. Collectively, these studies showed that these NK-like T cells are predominantly αβ + CD8 + with memory phenotype and could recognize HLA-E associated viral peptides after expansion upon TCR engagement. However, their clonality, transcriptome, regulation, specificity, and memory response in human have not been fully elucidated. We hypothesize that these NK-like T cells are phenotypically and functionally distinct from conventional T and NK cells and they play unique roles in virus and cancer control. Herein, we extensively characterized the CD56 + T cells and the KIR + T subset by analysis of TREC, TCRVβ spectrum, telomere length, surface biomarkers, genome-wide transcriptome, multi-analyte cytokine profiling, cancer cell susceptibility, tetramer staining, and real-time response to CMV reactivation in stem cell transplant recipients. In contrast to CD56 – T cells, CD56 + T cells are limited in TREC, TCRVβ, telomere length, cytokine secretion, transcription of metabolic genes stx6 , nnt , galnt2, hvcn1, tyms , rpa1 tmf1, ecop , and tspan3 , and are mostly KIR + , CD8 + , DNAM1 + , NKG2D + , CD44 + , NKp46 – and CD25 – . Compared to KIR – CD56 + T cells, KIR + CD56 + T cells are even more limited in TREC, TCRVβ, telomere length, and cytokine secretion, but have elevated transcription of NK cytotoxicity-related genes arrb1, ppp3cc , and lamc3 , higher degranulation after activation by IL-2/IL-15 and CD3/CD28 antibodies, better killing of cancer cells after cytokine priming, and are mostly KIR2DL2/3 + , NKG2D + , NKp46 + , CD16 + , NKG2C + , CD57 + , and 2B4 + . Importantly during CMV reactivation after stem cell transplantation, the percentage of KIR + CD56 + T cells in the patient9s blood increased dramatically and was significantly higher ( p =0.0021) than in those without viral reactivation. Ex vivo, KIR + CD56 + T cells demonstrate CMVpp65 tetramer staining, memory response to CMV peptides, and potent lysis of CMVpp65-pulsed target cells dependent on both KIR and TCR specificity. Furthermore, we identified for the first time that KIR – CD56 + T cells are Rorc + IL-13-secretor. In conclusion, both CD56 + and KIR + NK-like T-cell subsets are unique in biological and clinical properties and have distinct roles in cancer and infection control. Disclosures: No relevant conflicts of interest to declare.