Human natural killer cell maturation defect supports in vivo CD56(bright) to CD56(dim) lineage development.

Two populations of human natural killer (NK) cells can be identified in peripheral blood. The majority are CD3(-)CD56(dim) cells while the minority exhibits a CD3(-)CD56(bright) phenotype. In vitro evidence indicates that CD56(bright) cells are precursors of CD56(dim) cells, but in vivo evidence is lacking.

Cytokine-driven regulation of NK cell functions in tumor immunity: role of the MICA-NKG2D system.

Natural killer (NK) cells are critical players during tumor growth control in immunocompetent hosts. These cells also establish a cross-talk with dendritic cells (DCs) and promote a Th1-mediated immunity. NKG2D is a pivotal receptor that directs the tumoricidal activity of NK cells through the recognition of a group of ligands such as MICA widely expressed on different tumors.

Intracellular expression of MICA in activated CD4 T lymphocytes and protection from NK cell-mediated MICA-dependent cytotoxicity.

MICA is a stress-regulated molecule recognized by the NK cell-activating receptor NKG2D. Previously, we demonstrated that MICA is induced on activated T cells but regulation by mitogenic cytokines and its biological consequences remain unexplored. Here, we show that IL-2, IL-4, and IL-15 but not TNF-alpha or IFN-alpha induced MICA expression in T lymphocytes present in peripheral blood mononuclear cells (PBMCs), as assessed by Western blot.

NF-kappa B regulates expression of the MHC class I-related chain A gene in activated T lymphocytes.

MHC class I-related chain A gene (MICA) is a stress-regulated, HLA-related molecule which exhibits a restricted pattern of expression. MICA protein is up-regulated on different tumor cells, and is recognized by the lectin-like NKG2D molecule expressed by cytotoxic gammadelta T lymphocytes, CD8+ alphabeta T lymphocytes, and NK cells. Although MICA is not expressed on resting lymphocytes, we demonstrated that it is induced on activated T cells.