We have shown that virus infections and interferon inducers stimulate natural killer (NK) cell activation, proliferation and accumulation in target organs such as liver, lung, and peritoneum. Also stimulated by viruses are cytotoxic T cells which may, like NK cells, have a large granular lymphocyte (LGL) morphology. A subclass of stimulated T cells is allospecific whereas others are virus-specific. We propose to examine NK/LGL and T/LGL accumulation in organs during infection or IFN stimulus, to determine whether this accumulation is due to chemotaxis or to in situ differentiation or proliferation, and to determine which organs (spleen or bone marrow) are the source of NK cells appearing in target organs. Rat and hamster monoclonal antibodies to mouse NK cells will be made from animals stimulated with an NK cell clone or purified mouse blast NK/LGL. These antibodies, as well as others already available, will be used to phenotype NK cells in different organs and at different stages of activation, to compare them with T/LGL, and to localize NK cells in organs by immunohistochemistry. The antibodies will also be used to define cell receptors involved in chemotaxis. The proposed experiments should help elucidate how NK cells respond to stimuli within an infected animal, such that they may effectively contribute to natural immunity.
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