The two aims of the present study are as follows: (1) The in vitro analysis of murine natural cell-mediated cytotoxicity (NCMC), especially NC and NK cells, which includes: (a) characterization of NCMC cells, especially NC, including definition of their surface phenotype and properties and production of long-term cell lines; (b) regulation of NCMC activity, especially genetic control and induction and/or augmentation of NCMC activity, especially by interleukins; (c) mechanisms of in vitro activity of NCMC; (d) characterization of susceptibleresistant tumor targets, especially cloned variants with differences in susceptibility to lysis, aiming at the definition of the target structures being recognized by NCMC effectors; and (e) correlation of the in vivo behavior of transplanted tumor target cells with their in vitro susceptibility to lysis, including their growth patterns in animals with NCMC deficiencies. (2) The in vivo analysis of tumor development and behavior in mice with spontaneous and/or induced deficiencies, especially NCMC: (a) using different chemical and viral carcinogens to determine tumor incidence and characteristics in animals with NC, NK, and/or other deficiencies; (b) studying the properties of the tumors arising in the above models, especially correlations with the NCMC deficiency of the host; and (c) completing the cycle by determining the effect of restoration of NCMC deficiency on tumor development. In essence, the study plans to continue the methodical and comprehensive reevaluation of the immunological surveillance concept, but as a non-thymus-dependent proposition, with the major stress on the NCMC system as the main candidate for being the mediator of such antitumor surveillance in mice. (SR)
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