Cyclosporin a Inhibition of Interleukin
نویسنده
چکیده
NK cell cytolytic activity is enhanced after exposure to IFN and/or IFN inducers in vitro (1, 2) and in vivo (3-6). In vitro, IFN induces NK cell cytotoxicity on a per cell basis (1, 2) . In vivo, IFN not only enhances the level of killing mediated by individual cells, but also induces the blastogenesis and proliferation of NK cells (3-6). NK cell blastogenesis is observed during viral infections at times coinciding with the production of antiviral IFNs (3-5), after treatment with the IFN-inducer, polyinosinic-polycytidylic acid [poly(I:C)]' (5, 6), and after in vivo administration ofexogenous IFN (6). We have extensively characterized NK cell blastogenesis and proliferation, and have documented the following changes in NK cells induced by exposure to IFN in vivo : (a) increased size (3, 4, 6) and decreased density (7); (b) increased sensitivity to the cell cycle-specific toxin, hydroxyurea (4); (c) entry into S and G2/M phases of the cell cycle (8, 9) ; (d) enhanced incorporation of the DNA precursor [3H]thymidine by cells directly mediating lysis of NK target cells (3, 6) ; and (e) increased total numbers of NK cells per spleen (9). Taken together, these results conclusively demonstrate the proliferation of NK cells in response to IFNs in vivo. It has not been possible, however, to directly support NK cell expansion in vitro with IFN, suggesting that IFN does not act directly as a growth factor for NK cells . Thus, IFN-induced NK cell expansion appears to involve an as yet unidentified endogenous mediator whose production, activation, and/or effectiveness in vivo is linked to IFN. The Tcell growth factor IL-2 can directly induce NK cell activation and proliferation in vitro (10-12) and in vivo (8), and is a candidate to mediate endogenous NK cell responses . IL-2 is a product of mature, activated T cells, and T cells are presumed to be the major physiological source of the factor. During virus infection, IL-2 is produced in vivo with kinetics corresponding to those of T cell activation
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