Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2.

Normal splenocytes that are cultured in the lymphokine, interleukin 2 (IL-2), for as short as 2 days develop lytic activity for fresh syngeneic natural killer-resistant tumor cells as well as natural killer-sensitive YAC cells in a 4-hr 51Cr release assay. Lymphokine-activated killer (LAK) cells do not lyse syngeneic fresh lymphocytes but do lyse syngeneic concanavalin A-induced lymphocyte blasts. Lysis is not due to the presence of lectin or xenogeneic serum and appears to be an intrinsic property of lymphocytes activated in IL-2. The activation appears universal in that lymphocytes from all strains of mice activated in this manner exhibited similar patterns of lysis for fresh tumor target cells. To characterize the cells responsible for this lysis, we analyzed the phenotypic expression of surface markers on these cells with depletion techniques using monoclonal antibody and complement. These studies indicate that the precursor of the LAK cell is Thy-1+ and nonadherent to plastic or nylon wool. Lysis of syngeneic tumor was inhibited when LAK cells were treated with an anti-Thy-1.2, or anti-Lyt-2.2 monoclonal antibody and complement but not with anti-Lyt-1.2 monoclonal antibody and complement, indicating that the observed lytic activity was due to a Thy-1+ Lyt-1-2+ cell. Furthermore, LAK cell-mediated lysis could be inhibited by the addition of anti-Lyt-2 or LFA-1 monoclonal antibody to cytotoxicity assays. Cold target inhibition analysis revealed that the syngeneic tumor cells were lysed by recognition of a determinant not present on normal lymphocytes or lymphocyte blasts. This lysis of fresh solid tumor cells by lymphoid cells grown in IL-2 may be of value in the study of tumor-host immunological interactions. The biological significance of tumor lysis by IL-2-activated cells requires further study.

[1]  R. Herberman,et al.  Natural killer cells. , 1986, Annual review of medicine.

[2]  I. Kimber.  Natural killer cells. , 1985, Medical laboratory sciences.

[3]  T. Eberlein,et al.  Simplified techniques for the isolation of alloreactive cell lines and clones with specific cytotoxic or proliferative activity. , 1983, Journal of immunological methods.

[4]  S. Rosenberg,et al.  Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells , 1983, The Journal of experimental medicine.

[5]  S. Rosenberg,et al.  Characterization of the lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with phytohemagglutinin. , 1983, Journal of immunology.

[6]  J. Wunderlich,et al.  Broadly reactive murine cytotoxic cells induced in vitro under syngeneic conditions. , 1982, Journal of immunology.

[7]  T. Eberlein,et al.  Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. , 1982, The Journal of experimental medicine.

[8]  S. Rosenberg,et al.  Lymphokine-activated killer cell phenomenon. Lysis of natural killer- resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes , 1982, The Journal of experimental medicine.

[9]  Z. Eshhar,et al.  Functional relationships of lymphocyte membrane structures probed with cytolysis and/or proliferation-inhibiting H35-27.9 and H35-89.9 monoclonal antibodies. , 1982, Advances in experimental medicine and biology.

[10]  P. Golstein,et al.  Inhibition of murine T cell‐mediated cytolysis and T cell proliferation by a rat monoclonal antibody immunoprecipitating two lymphoid cell surface polypeptides of 94000 and 180000 molecular weight , 1982, European journal of immunology.

[11]  S. Rosenberg,et al.  Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. , 1981, Cancer research.

[12]  N. Minato,et al.  On the heterogeneity of murine natural killer cells , 1981, The Journal of experimental medicine.

[13]  T. Eberlein,et al.  In vitro growth of murine T cells. VI. Accelerated skin graft rejection caused by adoptively transferred cells expanded in T cell growth factor. , 1981, Journal of immunology.

[14]  S. Rosenberg,et al.  A simplified method for the production of murine T-cell growth factor free of lectin. , 1981, Journal of immunological methods.

[15]  R. Thorn.  Murine T-cell-mediated cytotoxicity against syngeneic and allogeneic cell lines induced by fetal calf serum. , 1980, Cellular immunology.

[16]  S. Rosenberg,et al.  In vitro growth of murine T cells. V. The isolation and growth of lymphoid cells infiltrating syngeneic solid tumors. , 1980, Journal of immunology.

[17]  S. Argov,et al.  Disappearance of the NK effect after explantation of lymphocytes and generation of similar nonspecific cytotoxicity correlated to the level of blastogenesis in activated cultures. , 1980, Journal of immunology.

[18]  F. Bach,et al.  Lysis of syngeneic solid tumor cells by alloantigen stimulated mouse T and non-T cells. , 1980, Journal of immunology.

[19]  G. Shearer,et al.  Xenogeneic serum-induced murine cytotoxic cells. I. The generation of effector components specific for self and allogeneic target cells. , 1979, Cellular immunology.

[20]  L. Herzenberg,et al.  Xenogeneic Monoclonal Antibodies to Mouse Lymphoid Differentiation Antigens * , 1979, Immunological reviews.

[21]  U. Hämmerling,et al.  Tumor necrosis serum induces a serologically distinct population of NK cells , 1979, The Journal of experimental medicine.

[22]  F. Bach,et al.  Continuous culture of T cells cytotoxic for autologous human leukaemia cells , 1979, Nature.

[23]  R. Kiessling,et al.  An Analysis of the Murine NK Cell as to Structure, Function and Biological Relevance , 1979, Immunological reviews.

[24]  O. Stutman,et al.  H–2 restriction and non-restriction of T-cell-mediated cytotoxicity against mouse mammary tumour targets , 1978, Nature.

[25]  O. Stutman,et al.  Natural cytotoxic cells against solid tumors in mice. I. Strain and age distribution and target cell susceptibility. , 1978, Journal of immunology.

[26]  S. Rosenberg,et al.  In vitro growth of murine T cells. II. Growth of in vitro sensitized cells cytotoxic for alloantigens. , 1978, Journal of immunology.

[27]  S. Rosenberg,et al.  In vitro growth of murine T cells. I. Production of factors necessary for T cell growth. , 1978, Journal of immunology.

[28]  O. Stutman,et al.  Natural cytotoxic cells against solid tumors in mice. II. Some characteristics of the effector cells. , 1978, Journal of immunology.

[29]  S. Rosenberg,et al.  In vitro growth of cytotoxic human lymphocytes. I. Growth of cells sensitized in vitro to alloantigens. , 1978, Journal of immunology.

[30]  O. Stutman,et al.  Ly phenotype of T cells cytotoxic for syngeneic mouse mammary tumors: evidence for T cell interactions. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Ortaldo,et al.  Cytotoxic reactivity of human lymphocytes cultured in vitro. , 1977, Journal of immunology.

[32]  T. Kishimoto,et al.  In vitro induction of polyclonal killer T cells with 2-mercaptoethanol and the essential role of macrophages in this process. , 1977, Journal of immunology.

[33]  S. Golub,et al.  Fetal calf serum-induced blastogenic and cytotoxic responses of human lymphocytes. , 1976, Cancer research.

[34]  T. Bradley.  STUDIES ON THE INDUCTION AND EXPRESSION OF T CELL‐MEDIATED IMMUNITY: V. LECTIN‐INDUCED NONSPECIFIC CELL‐MEDIATED CYTOTOXICITY BY ALLOIMMUNE LYMPHOCYTES , 1976, Transplantation.