NK Cell Subsets Isolated From Human Thymus Differ From Peripheral Blood NK Cells in Their Cytotoxic and Cytokine Secreting Capability

Abstract 1053

Until recently, studies on human NK cells have been mainly focused on NK cells from peripheral blood. Little is known about the functional role of human NK cell subpopulations in different lymphoid organs. We therefore aimed to characterize the phenotypical and functional profile of human NK cell subsets from different organs with a special focus on early forms of thymic NK cells in comparison to mature peripheral blood NK cells from adults and children.

Human NK cells can be classified according to the expression of CD56 and CD16 into immunoregulatory, cytokine producing CD56^highCD16^dim and mature cytotoxic CD56^dimCD16^high NK cells. It is widely accepted that NK cell development takes place in secondary lymphoid tissues leading to the maturation from CD56^highCD16^dim into CD56^dimCD16^high NK cells. Additionally, it has been reported that thymic CD34+ cells can differentiate into NK cells under treatment with IL-2 in vitro.

Here we report for the first time on a different composition of human NK cell subpopulations in the thymus compared to peripheral blood. NK cells isolated from the thymus did not only express lower levels of CD56 but also showed a different ratio of CD16^high/CD16^dim NK cells compared to peripheral blood NK cells. Extensive phenotypical analysis revealed significant alterations in expression patterns of killer-cell immunoglobulin-like receptors, natural cytotoxicity receptors and other maturation or differentiation markers on thymic NK cells. Functional analyses showed that the whole NK cell population from thymus as well as from peripheral blood of young children produced only low amounts of IFN-γ compared to adult peripheral blood NK cells.

Furthermore, functional assays of sorted NK cell subsets revealed important differences of CD16^high and CD16^dim thymic NK cells. Upon stimulation with IL-2 +/− K562 tumor cells, thymic CD16 ^high NK cells gain cytokine producing capacity, while CD16^dim develop a tumor killing capacity comparable to naive peripheral blood NK cells.

In summary, this comparative study of NK cell subsets provides important information on the development and function of NK cells that may be of great value for the optimization of cellular immune therapy.