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Induction of lymphokine-activated killer activity by interleukin 4 in human lymphocytes preactivated by interleukin 2 in vivo or in vitro. 1989

C M Higuchi, and J A Thompson, and C G Lindgren, and S Gillis, and M B Widmer, and D E Kern, and A Fefer
Department of Medicine, University of Washington School of Medicine, Seattle 98195.

In an attempt to augment the generation of human cytotoxic effector cells for potential cancer therapy with interleukin 2 (IL2) and lymphokine-activated killer (LAK) cells, the effect of interleukin 4 (IL4) on LAK cell induction was studied. In normal human peripheral blood lymphocytes (PBL), IL4 does not induce LAK activity and inhibits LAK induction by IL2. However, since lymphocyte activation, such as with antigen or mitogen, can render them responsive to IL4, the ability of IL4 to induce LAK activity in lymphocytes preactivated in vivo or in vitro with IL2 was investigated. PBL obtained from 12 patients with advanced cancer 1 to 3 days after IL2 therapy and from eight healthy control subjects were cultured 4 to 5 days with or without IL4 and/or IL2 and then tested for LAK activity as assessed by lysis of Daudi in a 4-h 51Cr release assay. In normal PBL, IL4 failed to induce LAK activity and consistently inhibited LAK induction by a suboptimal concentration of IL2 (10 units/ml). By contrast, IL4 induced LAK activity in PBL from seven of twelve IL2-treated patients and augmented LAK induction by the suboptimal IL2 in PBL from five of twelve IL2-treated patients. With an optimal LAK-inducing concentration of IL2 (1000 units/ml), IL4 less consistently inhibited LAK induction in normal PBL and had a variable effect upon LAK induction in PBL from IL2-treated patients. IL4 induced LAK activity in PBL obtained from a cancer patient after, but not before, systemic IL2 therapy. Similarly, IL4 induced LAK activity in normal PBL only after they had been preincubated with IL2. Thus, IL4 induces LAK activity in lymphocytes preactivated by IL2 in vivo or in vitro. Fluorescence-activated cell sorting revealed that the LAK activity, whether induced by IL4 or by IL2, was mediated largely by non-T (CD5-) natural killer-like (CD56+) cells. The results suggest a regulatory relationship between IL2 and IL4 in the induction and/or maintenance of LAK activity, which might be exploited to augment the generation of cytotoxic cells for lymphokine-mediated immunotherapy of human cancer.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D003602 Cytotoxicity, Immunologic The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement. Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000943 Antigens, Differentiation Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation. Differentiation Antigen,Differentiation Antigens,Differentiation Antigens, Hairy Cell Leukemia,Differentiation Marker,Differentiation Markers,Leu Antigen,Leu Antigens,Marker Antigen,Marker Antigens,Markers, Differentiation,Antigen, Differentiation,Antigen, Leu,Antigen, Marker,Antigens, Leu,Antigens, Marker,Marker, Differentiation
D000945 Antigens, Differentiation, T-Lymphocyte Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function. Antigens, Differentiation, T-Cell,Differentiation Antigens, T-Cell,L3T4 Antigens,Leu Antigens, T-Lymphocyte,T-Cell Differentiation Antigens,T-Lymphocyte Differentiation Antigens,T6 Antigens,Antigens, Differentiation, T Lymphocyte,Differentiation Antigens, T Lymphocyte,Antigens, L3T4,Antigens, T-Cell Differentiation,Antigens, T-Lymphocyte Differentiation,Antigens, T-Lymphocyte Leu,Antigens, T6,Differentiation Antigens, T Cell,Differentiation Antigens, T-Lymphocyte,Leu Antigens, T Lymphocyte,T Cell Differentiation Antigens,T Lymphocyte Differentiation Antigens,T-Lymphocyte Leu Antigens
D015703 Antigens, CD Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation. CD Antigen,Cluster of Differentiation Antigen,Cluster of Differentiation Marker,Differentiation Antigens, Leukocyte, Human,Leukocyte Differentiation Antigens, Human,Cluster of Differentiation Antigens,Cluster of Differentiation Markers,Antigen Cluster, Differentiation,Antigen, CD,CD Antigens,Differentiation Antigen Cluster,Differentiation Marker Cluster,Marker Cluster, Differentiation
D015847 Interleukin-4 A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells. B-Cell Growth Factor-I,B-Cell Stimulatory Factor-1,Binetrakin,IL-4,Mast Cell Growth Factor-2,B Cell Stimulatory Factor-1,B-Cell Growth Factor-1,B-Cell Proliferating Factor,B-Cell Stimulating Factor-1,B-Cell Stimulatory Factor 1,BCGF-1,BSF-1,IL4,MCGF-2,B Cell Growth Factor 1,B Cell Growth Factor I,B Cell Proliferating Factor,B Cell Stimulating Factor 1,B Cell Stimulatory Factor 1,Interleukin 4,Mast Cell Growth Factor 2
D015979 Killer Cells, Lymphokine-Activated Cytolytic lymphocytes with the unique capacity of killing natural killer (NK)-resistant fresh tumor cells. They are INTERLEUKIN-2-activated NK cells that have no MAJOR HISTOCOMPATIBILITY COMPLEX restriction or need for antigen stimulation. LAK cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients. LAK Cells,Lymphokine-Activated Killer Cells,Cell, LAK,Cell, Lymphokine-Activated Killer,Cells, LAK,Cells, Lymphokine-Activated Killer,Killer Cell, Lymphokine-Activated,Killer Cells, Lymphokine Activated,LAK Cell,Lymphokine Activated Killer Cells,Lymphokine-Activated Killer Cell
D018956 CD5 Antigens Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156) Antigens, CD5,CD5 Antigen,Leu-1 Antigen,T1 Antigen,Antigen, CD5,Leu 1 Antigen

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