Kinetics of NK cell activity during tumor development in a mouse model
Publication Type:Journal Article
Source:Cancer Journal, Volume 4, Number 2, p.97-102 (1991)
Keywords:animal model, animal tissue, article, chromium 51, cytotoxicity, dalton lymphoma, interleukin 2, lymphocyte, mouse, natural killer cell, nonhuman, priority journal, T cell lymphoma, unclassified drug
We have previously reported the profiles of natural killer cell mediated cytotoxicity (NKC/MC) in the spleen cells of tumor bearing Balb/c mice during the development of Dalton's lymphoma ascites (DLA) tumor, a murine T cell lymphoma. In the present paper we have used two different methods of assessing NK cytotoxicity in vitro to dissect the relative importance of various steps involved in attaining the overall result. The 51Cr release assay has been combined with a recently established single cell conjugate assay using poly-L-lysine coated coverslips to allow better quantitative analysis. With this double procedure we could estimate the percentage of active killer cells, V(max) and recycling capacity of the effector cells at different intervals of tumor progression. A large granular lymphocyte (LGL) enriched population obtained by discontinuous density gradient centrifugation of Percoll was used as effector cells against the murine NK susceptible target YAC-1 in both assays. Also, the ability of the effector cells to release natural killer cytotoxic factor (NKCF), on stimulation with YAC-1 cells was estimated in a micro-supernatant assay of 48 h. A significant enhancement in the number of active killer cells coupled with increased NKCF production was observed on day 7 and day 12 after tumor inoculation with respect to normal control. A decline in NKCWC observed at the advanced stage of tumor growth (day 19) was found to be associated with diminished NKCF production as well as a reduced number of active killer cells among the effector cell population. Estimated maximal recycling capacity showed minimal differences at different phases of tumor growth. Pretreatment of day-19 effector cells with 200 IU/ml of human recombinant IL-2 resulted in augmentation of NKCMC, V(max), percentage active killer cells, and NKCF production.
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