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In T and NK cells the IL-15 receptor includes IL-2\/15R\u03b2 and \u03b3<jats:sub>c<\/jats:sub>, subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15R\u03b1. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2\/STAT5 activation rather than the Jak1\/Jak3 and STAT5\/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. 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