However, NK cells also produce several cytokines and their role a

However, NK cells also produce several cytokines and their role as mediators in regulating innate and adaptive immune response is a main topic of current research 1–6. Human NK cells Inhibitor Library mw are defined as CD3−CD56+, whereas murine NK cells, which lack CD56, are discriminated as CD3−NK1.1+. Recently, NKp46 (CD335) has been identified as a common marker for NK cells in both species, simplifying the future definition of NK cells 7. In contrast to other lymphocytes, it is mainly the balance of activating and inhibitory signals, mediated by respective receptors, that regulates NK-cell function 8. Human NK cells express two structurally unrelated MHC class I-specific receptor families, the killer

cell immunoglobulin-like receptors (KIR) and the killer cell lectin-like receptors (KLR). Mouse NK cells lack KIR, but they possess functional homologues with a lectin-like structure (Ly49 receptors). Research over the last two decades has revealed that NK cells do not represent a homogeneous

lymphocyte fraction but can be subdivided into functionally distinct populations 9–13. In humans, the two common NK-cell subsets are defined according to the density of the surface marker CD56. As reviewed in Wilk et al.14, CD56dim NK cells represent the classical cytotoxic NK-cell subset, whereas CD56bright NK cells exert only marginal cytotoxic capacity and produce higher amounts of cytokines such as IFN-γ and TNF-α 14, 15. The predominant function of CD56bright NK cells as cytokine producers indicates a primary role of these see more cells in immune regulation. Recently, a new approach to categorize NK cells by differentiating between “target cell responsive” and “cytokine responsive” has been proposed 16. The proportions of the NK-cell subsets vary between the different compartments of the body. For instance, the ratio of CD56dim and CD56bright NK cells in peripheral blood is inverted in LN (ca. 10:1 in blood versus ca. 1:10 in LN) 12, 17, 18. The particular phenotype of decidual NK cells (CD56superbrightKIR+) Pregnenolone also hints to a specialized “equipment” of NK cells in certain locations

18–20. The lack of identical or comparable surface molecules is a major obstacle when transferring information from mouse models to human biology. Several attempts have been made to find markers defining mouse NK-cell subsets equivalent to those in humans. Murine IFN-γ-producing killer DC with a B220+CD11c+NK1.1+ phenotype are suggested to belong to the NK-cell lineage and overlap with human CD56bright NK cells in cytokine production and lymphoid tissue distribution. However, lysis of YAC-1 target cells did not differ from CD11c− NK cells 21. Recent data indicate CD127 as a potential marker for murine thymic NK cells that correspond to the human CD56bright NK-cell subset 22. Currently, CD27 is discussed as a potential NK-cell subset marker for murine as well as for human NK-cell subsets since CD27 is almost exclusively expressed on CD56bright NK cells.

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