Morphology, topography, and immunohistochemical features of leukocyte infiltrates were studied in various sites of the liver samples from the patients with metastatic disease, been affected by hepatitis B and C viruses at different degree of activity. Liver of СВА mice with implanted САО-1 tumour was also under study. Histochemical, and functional features, as well as immune phenotype of these cells were investigated. It has been shown that the major fraction of leukocyte infiltrates, mostly associated with implanted tumours in experimental mice, and in the areas adjacent to the tumor in humans, like as on the peak of viral hepatitis activity, is composed of lymphocytes. They are presented by large numvers of activated proliferating and differentiating cells bearing specific antigens, as well as natural killers and T-lymphocytes, possessing high-level killer activity towards NK-sensitive, and autologous lines of cancer cells. Hence, the results of our study, generally, confirm the data from literature reporting on existence of a special lymphocyte subpopulation, NKT cells, in human or murine liver affected by hepatitis virus or malignant tumors. The data concerning functional properties of these cells may be used for development of immunotherapy methods of viral diseases and oncological conditions complicated by liver metastases.

Abstract. The effects of 'Profetal', a drug containing liophylized, dextran-stabilized human alpha-fetoprotein as main active component, were investigated on peripheral donor blood mononuclear leukocytes (ML), with respect to their functional properties and the potential to generate mature dendritic cells (DC). Addition of the drug to cell cultures at optimal doses was shown to cause significant increase in their proliferative capacity and ML blastic transformation levels, and enhanced cytotoxicity towards K562 tumor cells, as well as to induce maturation of antigen-presenting dendritic cells. On the basis of the data obtained, a conclusion is made that 'Profetal' is an active immunomodulatory factor, and it may be applied for generation of cytotoxic lymphocytes and mature DC, aiming to apply them for the biotherapy of oncological and infectious diseases.

AIM:To study the ability to induce dendritic cells maturation obtained from bone marrow of mice by staphylococcal complex of antigens containing bacterial ligands for Toll-like receptors (lipopeptides, lipoproteins, and peptidoglycans).MATERIALS AND METHODS:Commercially available TNF-alpha, inductors ofdendritic cells (DCs) maturation, as well C57/BL line mice were used for the study. Immunophenotype of DCs was assessed by flow cytometry and monoclonal antibodies against cellular antigens. Cytological study using phase-contrast microscopy as well as electron microscopy were performed. Levels of cytokines were measured by ELISA.RESULTS:Obtained DCs had typical morphologic characteristics of mature cells. However the culture was still heterogenous with presence of macrophages that was evident from immunophenotype of obtained cells: CD34(-/+), CD38+, CD40+, CD80+, CD86+, MHC II+, F4/80(-/+). Number of TLR2-expressing cells was also reliably increased in culture of DCs that confirms the presence of corresponding ligands binding with this type of receptor in the preparation. Application of each studied preparation resulted in synthesis of large amount of TNF-alpha, IL-6, IL-1beta, IL-12 by DCs, and IFN-gamma by several types of them (RP and CB24). Although the intensity of induced cytokine synthesis varied for each preparation, it was many times higher compared with immature DCs.CONCLUSION:High synthesis level and wide spectrum of cytokine production demonstrated that under the influence of bacterial ligands DCs acquired characteristics needed for effective antigen presentation and priming of immune response.

Immunosupressive activity of cyclophosphan was evaluated at Wistar CBA mice. Injection of cyclophosphan induced a significant decrease of lymphocytes in peripherial blood samples and in spleen; subpopulations of lymphocytes were changed and its functional activity was reduced. Immunovak VP-4, bacterial immunomodulator, rapidly corrects cyclophosphan-induced changes. The observed effect may play a significant role at prevention of infectious complications after chemotherapy-induced immunosuppression. Based on the above mentioned data that Immunovak is capable to stimulate antiinfectious and antitumour immune response we conclude that it is important to perform clinical trial to investigate Immunovak VP-4 capability to prevent immune response failure after chemotherapy.

Cytotoxic activity of lymphokine-activated killers (LAK) with respect to various tumor lines has been studied. It has been shown that LACs act like natural killers and they are able to effect selectively on tumor cells. They have a high killer ability and wide spectrum of cytotoxic activity towards various types of transformed cells. These findings are of great importance for administering IL-2/LAK therapy for various nosological forms and for cancer biotherapy as well.