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Title: Action of T-activin on activity of human natural killer cells in vitro

Abstract

This paper describes a study of the action of T-activin on activity of human natural killer cells (NKC) in vitro. The K-562 chronic human myeloid leukemia cells, cultured in vitro, used as targets were labeled with /sup 3/H-uridine. The experimental results indicate that T-activin can depress NKC activity but under certain conditions, it can also stimulate NKC. T-activin possesses immunoregulatory properties relative to NKC activity in vitro.

Authors:
; ; ; ;
Publication Date:
Research Org.:
N. I. Pirogov Second Moscow Medical Institute, USSR
OSTI Identifier:
5563541
Resource Type:
Journal Article
Resource Relation:
Journal Name: Bull. Exp. Biol. Med. (Engl. Transl.); (United States); Journal Volume: 101:4; Other Information: Translated from Byulleten' Ehksperimental'noj Biologii i Meditsiny; 101: No. 4, 455-457(Apr 1986)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; IMMUNOSUPPRESSIVE DRUGS; BIOLOGICAL EFFECTS; LEUKOCYTES; CELL KILLING; IMMUNE REACTIONS; RADIOIMMUNOASSAY; MAN; MYELOID LEUKEMIA; TUMOR CELLS; BIOLOGICAL FUNCTIONS; DOSE-RESPONSE RELATIONSHIPS; INHIBITION; LABELLING; LYMPHOCYTES; SCINTILLATION COUNTING; THYMUS; TRITIUM COMPOUNDS; URIDINE; ANIMAL CELLS; ANIMALS; AZINES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CONNECTIVE TISSUE CELLS; COUNTING TECHNIQUES; DISEASES; DRUGS; FUNCTIONS; HEMIC DISEASES; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; IMMUNOASSAY; IMMUNOLOGY; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; LEUKEMIA; LYMPHATIC SYSTEM; MAMMALS; MATERIALS; NEOPLASMS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PRIMATES; PYRIMIDINES; RADIOASSAY; RADIOIMMUNOLOGY; RIBOSIDES; SOMATIC CELLS; TRACER TECHNIQUES; URACILS; VERTEBRATES; 550301* - Cytology- Tracer Techniques; 550901 - Pathology- Tracer Techniques

Citation Formats

Cheknev, S.B., Saidov, M.Z., Koval'chuk, L.V., Pavlyuk, A.S., and Arion, V.Ya.. Action of T-activin on activity of human natural killer cells in vitro. United States: N. p., 1986. Web. doi:10.1007/BF00834421.
Cheknev, S.B., Saidov, M.Z., Koval'chuk, L.V., Pavlyuk, A.S., & Arion, V.Ya.. Action of T-activin on activity of human natural killer cells in vitro. United States. doi:10.1007/BF00834421.
Cheknev, S.B., Saidov, M.Z., Koval'chuk, L.V., Pavlyuk, A.S., and Arion, V.Ya.. 1986. "Action of T-activin on activity of human natural killer cells in vitro". United States. doi:10.1007/BF00834421.
@article{osti_5563541,
title = {Action of T-activin on activity of human natural killer cells in vitro},
author = {Cheknev, S.B. and Saidov, M.Z. and Koval'chuk, L.V. and Pavlyuk, A.S. and Arion, V.Ya.},
abstractNote = {This paper describes a study of the action of T-activin on activity of human natural killer cells (NKC) in vitro. The K-562 chronic human myeloid leukemia cells, cultured in vitro, used as targets were labeled with /sup 3/H-uridine. The experimental results indicate that T-activin can depress NKC activity but under certain conditions, it can also stimulate NKC. T-activin possesses immunoregulatory properties relative to NKC activity in vitro.},
doi = {10.1007/BF00834421},
journal = {Bull. Exp. Biol. Med. (Engl. Transl.); (United States)},
number = ,
volume = 101:4,
place = {United States},
year = 1986,
month = 9
}
  • The sensitivity of human natural killer cell activity after exposure of peripheral blood mononuclear cells to different doses of gamma irradiation was examined in a group of healthy adults and several families. Theee patterns of radiation sensitivity were observed: (1) loss of all NK activity after 3000 rads irradiation; (2) loss of approximately 50% of the NK activity; and (3) maintenance of activity after this dose of irradiation. Low dose irradiation (500 to 2000 rads) resulted in an enhancement of activity. The radiation dose giving low dose activation reflected the individual's sensitivity to 3000 rads. Population studies and the segregationmore » in two informative families indicate that radiation sensitivity of NK activity is controlled by x-linked codominant genes.« less
  • In vitro exposure of human peripheral blood mononuclear cells (PBMC) to ultraviolet B (uvB) radiation has been shown to inhibit natural killer (NK) cell-mediated cytotoxicity in a dose-dependent fashion. The purpose of this study was to examine the manner by which uvB produced these deleterious effects. Inhibition of NK activity was not due to lethal injury to NK cells since the viability of cell populations enriched for NK activity was greater than 90% with the uvB doses employed. uvB appeared to directly affect NK cells since procedures which removed suppressor mechanisms, such as removal of monocytes and pharmacologic inhibition ofmore » the cyclooxygenase pathway, failed to reverse the response. Furthermore, no suppression of activity of unirradiated NK cells could be produced by coincubation of unirradiated NK cells with uv-irradiated NK cells. When the single cell assay for binding and killing was employed to determine at which stage in the lytic sequence inhibition occurred, it was found that binding was normal but lysis of bound targets and the recycling capacity of active NK cells were markedly reduced. At uvB doses above 50 J/m2, both interferon alpha (IFN-alpha) and interleukin 2 (IL-2) were ineffective in augmenting NK cell-mediated cytotoxic reactions after cells had been irradiated with uvB. Furthermore, incubation of NK cells with IFN-alpha prior to irradiation failed to protect against the inhibitory effects. These studies provide evidence that in vitro exposure of NK cells to uvB radiation inhibits their function by a direct nonlethal effect and that this inhibition occurs selectively at the postbinding stage of target cell lysis.« less
  • On analysis of in vitro assays of human natural killer (NK) cell function the inadequacy of commonly used methods of expressing lytic activity was apparent. A comparison was made of the data obtained using modifications of two equations-the simple exponential fit and the von Krogh equations. Both of these equations were found to satisfy the following essential criteria for use in these assays. First, the majority of the results obtained in the chromium-release assay could be used in data reduction; second, the resultant ''dose-response'' curve was reduced to linearity; and third, a single numerical expression was obtained which was directlymore » proportional to the cytotoxic activity. Of the two methods the more conventional exponential fit was found to be the simpler to use. The closeness of fit of the experimentally derived data to the ideal curves did not support the possibility that normal lymphocyte preparations contain suppressor cells capable of inhibiting NK activity. Data have also been presented showing that NK-sensitive targets could be categorized with respect to their susceptibility by comparing the slopes of the target cell survival curves obtained using the exponential fit equation. These observations are relevant to the accurate assessment of NK activity in patient populations and to the determination of the effects of disease and its treatment on this activity.« less
  • The sensitivity of human natural killer (NK) cell activities (both binding and killing) after exposure of peripheral blood mononuclear cells to different doses of gamma radiation was studied. A panel of monoclonal antibodies was used to identify the NK and T-lymphocyte subsets and to evaluate their radiosensitivity. Peripheral blood mononuclear cells were irradiated with low (2-6 Gy) and high (10-30 Gy) doses and NK cell binding and cytotoxic activity against K562 target cells were studied after 3 h and 48 h in culture. The primary damage to NK cell activity was identified at the postbinding level and affected mainly themore » lytic machinery. After 48 h culture postirradiation, an overall depression of cytotoxic activity was observed, but ionizing radiation produced either a selection of the more cytotoxic NK cell subsets, which therefore might be considered more resistant to radiation damage than the less cytotoxic NK cells, or a long-term stimulation of cytotoxic activity in surviving cells.« less
  • Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2more » was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.« less