Cytotoxic activity of lymphocytes isolated from mouse liver involved into tumor process.

We studied cytotoxic activity and immunophenotype of mononuclear cells isolated from the liver of mice after implantation of ovarian cancer cells into the liver parenchyma. The isolated cells exhibited higher natural killer cell activity and possessed higher cytotoxic potential against autologous tumor cells compared to spleen lymphocytes. The ratio of CD3+ lymphocytes and natural killer cells was high in the liver with tumor metastases. Lymphoid cells were practically absent in the liver of intact animals. Natural killer cells and T cells from liver tumor tissue play an important role in antitumor immunity and can be used for local and regional adjuvant immunotherapy of liver metastases.

[Generation of dendrite cells and the use of immunomodulators of bacterial origin as cell differentiation inducers].

The generation of ripe dendrite cells (DC) of marrow origin was obtained with the use of the vaccine Immunovac-BN-4, an immunomodulator of microbial origin, as well as Klebsiella pneumoniae LPS and TNF-alpha, as ripening inducers. These inducers equally led to the ripening of DC. The generation of ripe DC was characterized by morphological, phenotypical and functional changes. The immunophenotype of cells altered from CD34+, CD38-, CD40-, CD80-, CD86-, MHC I-, MHC II-, F4/80- to CD34-, CD38+, CD40+, CD80+, MHC I+, MHC II+, F4/ 80(low). In parallel with the ripening of DC their phagocytic activity decreased. In culture medium with ripe DC the levels of such cytokines as IL-1b, IL-6, IL-12, IFN-gamma, TNF-alpha significantly increased and the production of IL-4 decreased. The content of IL-2 and IL-10 remained unchanged.

[Influence of dendrite cells, generated with the use of immunomodulators of microbial origin, on the proliferative and cytotoxic activity of lymphocytes].

The influence of ripe dendrite cells (DC) on the proliferative activity of mononuclear leukocytes and the cytotoxic activity of lymphocytes of syngenic mice was studied. As inducers of DC ripening, the combination of antigenic components incorporated into the vaccine "lmmunovac Bh-4", (Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Staphylococcus aureus), as well as K. pneumoniae LPS and TNF-alpha, were used. This study demonstrated that DC activated with these preparations enhanced the proliferative activity of mononuclear leukocytes, the activity of Bh-4 being higher than that of K. pneumoniae LPS. The increase of proliferative activity was accompanied by a rise in the cytotovicity of mouse lymphocytes with respect to the NK-sensitive tumor line YAC-1 or Ehrlich tumor cells. The incubation of the lymphocytes with ripe DC (with the use of the preparations under study as ripening inducers), loaded with tumor antigens, made it possible to obtain cytotoxic lymphocytes having high cytotoxic activity with respect, mainly, to those tumor lines from which lysates for the treatment of DC had been produced. The activation of DC with bacterial immunomodulators led to an increase in the antigen-presenting function of these cells, to their higher capacity for regulating the differentiation of mononuclear leukocytes and for activating the cytotoxicity of natural killers.