Biomaterial Database

Interleukin-12 is a costimulatory cytokine for leukemic CD3+ large granular lymphocytes. 1995

T C Gentile, and T P Loughran

Department of Medicine, State University of New York at Syracuse 13210, USA.

The activation signals leading to proliferation of leukemic CD3+ large granular lymphocytes (LGL) are incompletely understood. In this study, the role of recombinant human interleukin-12 (rhIL-12) alone or in combination with other activation signals was studied in vitro. Anti-CD3 monoclonal antibody (MoAb) alone caused marked stimulation of peripheral blood mononuclear cells (PBMC) from three CD3+ LGL leukemic patients, whereas rhIL-12 alone had less effect as measured in a [3H]thymidine incorporation assay. The combination signals of anti-CD3 MoAb and rhIL-12 produced a proliferative response greater than anti-CD3 MoAb alone or rhIL-12 alone. Leukemic LGL, purified by CD8+ affinity chromatography, showed similar proliferative responses as PBMC from LGL leukemic patients, suggesting that the observed effect was indeed due to direct stimulation of leukemic LGL. Radiolabeled IL-12 binding studies demonstrated that anti-CD3 MoAb upregulated the number of IL-12 receptors per cell on PBMC from these patients. Neutralizing antibody to rhIL-12 partially blocked the proliferative response to anti-CD3 MoAb suggesting involvement of IL-12 in the pathway of activation of leukemic LGL via stimulation of the T cell receptor (TCR) (mimicking activation by antigen). These results show that IL-12 acts as a costimulatory cytokine for proliferation of leukemic LGL activated through the TCR in vitro.

UI	MeSH Term	Description	Entries
D007694	Killer Cells, Natural	Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.	NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D007945	Leukemia, Lymphoid	Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.	Leukemia, Lymphocytic,Lymphocytic Leukemia,Lymphoid Leukemia,Leukemias, Lymphocytic,Leukemias, Lymphoid,Lymphocytic Leukemias,Lymphoid Leukemias
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
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
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
D016176	T-Lymphocyte Subsets	A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.	T-Cell Subset,T-Cell Subsets,T-Lymphocyte Subset,Subset, T-Cell,Subset, T-Lymphocyte,Subsets, T-Cell,Subsets, T-Lymphocyte,T Cell Subset,T Cell Subsets,T Lymphocyte Subset,T Lymphocyte Subsets
D017252	CD3 Complex	Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).	Antigens, CD3,CD3 Antigens,T3 Antigens,CD3 Antigen,T3 Antigen,T3 Complex,Antigen, CD3,Antigen, T3,Antigens, T3
D018664	Interleukin-12	A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.	Edodekin Alfa,IL-12,Natural Killer Cell Stimulatory Factor,Cytotoxic Lymphocyte Maturation Factor,IL 12,IL-12 p70,IL12,Interleukin 12,Interleukin-12 p70,Interleukin 12 p70