Transduction of cytotoxic signals in natural killer cells: a general model of fine tuning between activatory and inhibitory pathways in lymphocytes.
NK-cells are 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 cells during antibody-dependent cell cytotoxicity (ADCC). Second, during natural cytotoxicity NK-cells are also able to recognize and to induce the lysis of a variety of target cells, 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 is a general decision mechanism which exists not only in T- and B-lymphocytes, but also in a variety of other hematopoietic cells.
Renard
V
V
Centre d'immunologie INSERM/CNRS de Marseille-Luminy, Marseille, France.
Cambiaggi
A
A
Vély
F
F
Bléry
M
M
Olcese
L
L
Olivero
S
S
Bouchet
M
M
Vivier
E
E
D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
D011971:Receptors, Immunologic