ABSTRACT
The proliferation activity of monolayer culture of Madin Darby Canine Kidney (MDSK) cells is suppressed by a thermostable protein factor of renal tissue of white rats and of humans. Under the influence of renal factors (RF), a decrease in cell number, and suppression of DNA synthesis and mitotic activity in MDCK cells occur. The inhibition of proliferative activity of cultured cells under the influence of RF was substantiated also by MTT assay. It was established that the inhibitory influence of RF is stipulated by suppression of RNA synthesis. It follows that RF may inhibit division of MDCK cells via suppression of gene expression in G1-phase. Similar factors were obtained from renal cells of different systematic groups of organisms (snail, frog, fish, pigeon, guinea pig, swine).
Subject(s)
Biological Factors/pharmacology , Epithelium/drug effects , Kidney/metabolism , Animals , Biological Factors/isolation & purification , Cell Line/physiology , Cell Proliferation/drug effects , DNA/biosynthesis , Dogs , Down-Regulation , Epithelium/physiology , Humans , Mitosis , TemperatureABSTRACT
It was demonstrated in in vivo and in vitro experiments that interleukin-2, obtained by cultivation of donor lymphocytes and purified by gel filtration, induces the production of mouse and human killer lymphocytes possessing high cytolytic activity against tumor cells. Interleukin-2 does not cause irreversible changes of the physiological and morphologic indices of vital activity in mice.
Subject(s)
Antineoplastic Agents , Interleukin-2/therapeutic use , Animals , Cytotoxicity Tests, Immunologic/methods , Drug Screening Assays, Antitumor , Female , Humans , Interleukin-2/isolation & purification , Interleukin-2/pharmacology , Interleukin-2/toxicity , Killer Cells, Lymphokine-Activated/drug effects , Killer Cells, Lymphokine-Activated/immunology , Leukemia P388/drug therapy , Leukemia P388/immunology , Lymphocytes/drug effects , Lymphocytes/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred DBA , Time Factors , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/immunologyABSTRACT
Specific cytolytic and natural killer activity of peripheral blood lymphocytes was studied in 12 patients with metastatic melanoma. The cytolytic activity of lymphocytes against autologous tumor cells was found in 8 patients. It appeared significantly enhanced by pretreatment of tumor target cells with concanavalin A (Con A). The natural killer activity in all the patients was 2-10 times as high as the specific cytolytic activity. Stimulation of patient lymphocytes with autologous tumor cells or with the mixture of lymphocytes from 5 allogeneic donors induced the generation of highly active T killers possessing natural killer and specific antitumor cytolytic activity.
Subject(s)
Melanoma/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Cells, Cultured , Cytotoxicity Tests, Immunologic , Female , Humans , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Lymphocyte Activation/drug effects , Lymphocyte Culture Test, Mixed , Male , Melanoma/secondary , Middle Aged , T-Lymphocytes, Cytotoxic/drug effectsABSTRACT
Interleukin-2 (IL-2) was isolated from donor peripheral blood lymphocytes and from JURKAT T-lymphoma cells. The purification procedure including gel filtration on DEAE and CM-Sephadex resulted in a 400-fold increase of the enzyme specific activity. It was shown that optimal proliferation of T-lymphocytes occurs upon consecutive treatment of cells with phytohaemagglutinin and IL-2 as well as in the presence of a serum. The properties and procedure of isolation of the long proliferating line of IL-2-dependent T-cells B-5 were described. Proliferation of B-5 cells completely depended on the presence of IL-2 in the medium, although long-term proliferation occurred upon periodic stimulation of cells with the antigen (allogenic lymphocytes). In the absence of IL-2 B-5 cells decay within 36 hours. The perspective uses of IL-2 prepared from the cultural fluid of human peripheral blood lymphocytes for adoptive immunotherapy of tumours and the applicability of IL-2-dependent B-5 cells for testing the activity of IL-2 preparations from various sources are discussed.
