Specific phenotype and function of CD56-expressing innate immune cell subsets in human thymus

Whereas innate immune cells, such as NK and innate lymphoid cells (ILCs), have been characterized in different human tissues, knowledge on the thymic CD56-expressing cell subsets is limited. In this study, the rare subpopulations of thymic CD56⁺CD3^- cells from samples of >100 patients have been successfully analyzed. The results revealed fundamental differences between thymic and peripheral blood (PB) CD56⁺CD3^- cells. Thymic tissues lacked immunoregulatory CD56^highCD16^dim NK cells but showed two Eomes⁺CD56^dim subsets on which common NK cell markers were significantly altered. CD56^dimCD16^high cells expressed high amounts of NKG2A, NKG2D, and CD27 with low CD57. Conversely, CD56^dimCD16^dim cells displayed high CD127 but low expression of KIR, NKG2D, and natural cytotoxicity receptors (NCRs). Thymic CD56⁺CD3^- cells were able to gain cytotoxicity but were especially immunoregulatory cells, producing a broad range of cytokines. Finally, one population of thymic CD56+ cells resembled conventional NK cells, whereas the other represented a novel, noncanonical NK subset.