Transduction of cytotoxic signals in natural killer cells: a general model of fine tuning between activatory and inhibitory pathways in lymphocytes

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Abstract
Summary: NK‐cells axe large granular lymphocytes, which are capable of exerting two major types of effector function, cell cytotoxicity and lymphokine secretion. NK ‐cells can exert cell cytotoxicity in one of two ways. First, NK‐cells are able to recognize and to induce the lysis of antibody‐coated target ceils during antibody‐dependent cell cytotoxicity (ADCC). Second, during natural cytotoxicity NK cells are also able to recoginze to induce the lysis of a variety of target cell, including primarily virus‐infected cells as well as tumor cells. Recently, a novel mechanism has been elucidated which controls NK‐cell‐activation programs and which is based on the cell surface expression of killer‐cell inhibitory receptors (KIR). We will review here the molecular dissection of this inhibitory signalling pathway which utilizes immunoreceptor tyrosine‐based inhibition motifs (ITIM) expressed in KIR intracytoplasmic domain. We will also show that this strategy used by NK‐cells to regulate their effector functions a general decision mechanism which exists not only in T‐ and B‐lymphocytes, but also in a variety of other hematopoietic cells.