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This is mediated by Ca 2+ -dependent granule exocytosis, cytotoxic proteins (perforin and granzymes) release from intracytoplasmic granules, constitutive or induced upon interaction with target cells FasL expression, Ca 2+ -independent Fas (CD95/Apo 1)-mediated apoptosis induction, and membrane-bound or secreted cytokines (e.g., TNF-) production [248]