Biomaterial Database

Effects of the Th1 and Th2 stimulatory cytokines interleukin-12 and interleukin-4 on human immunodeficiency virus replication. 1995

A Foli, and M W Saville, and M W Baseler, and R Yarchoan

Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

The cytokines interleukin-12 (IL-12) and IL-4 play important roles in the development of Th1-like (type-1) and Th2-like (type-2) T-cell responses, respectively, and there is evidence that type-1/type-2 T helper imbalances are important in the pathogenesis of human immunodeficiency virus (HIV) disease. With this background, we examined the effects of these cytokines on HIV replication. Neither stimulated HIV replication in fresh peripheral blood mononuclear cells (PBMC). However, in prestimulated PBMC, IL-12, and to a greater extent, IL-4 as well as IL-2, induced production of HIV p24 antigen over 7 days of culture (no cytokine 3,900 x/divided by 1.31 [GM x/divided by SEM] pg/mL; IL-12, 34,300 x/divided by 1.39 pg/mL; IL-4, 283,000 x/divided by 1.14 pg/mL; and IL-2, 328,000 x/divided by 1.31 pg/mL). Neither IL-12- nor IL-4-induced HIV replication was attributable to induction of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, or TNF-beta. Both IL-12- and IL-4-induced HIV replication was associated with selective loss of the CD4+ subset in stimulated cultures. IL-4 stimulated HIV replication in monocyte/macrophages, while IL-12 had little or no effect in these cells. Finally, HIV replication stimulated by IL-12 or IL-4 was inhibited by dideoxynucleosides. Thus, IL-12 and IL-4 enhance HIV replication and HIV-induced cell death in prestimulated PBMC. Through killing of the CD4+ T cells stimulated by these cytokines, this may result in inappropriate type-1/type-2 responses in HIV-infected patients and contribute to their Th1 immunodeficiency.

UI	MeSH Term	Description	Entries
D007378	Interleukins	Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.	Interleukin
D007963	Leukocytes, Mononuclear	Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.	Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
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
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009000	Monocytes	Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.	Monocyte
D010835	Phytohemagglutinins	Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.	Kidney Bean Lectin,Kidney Bean Lectins,Lectins, Kidney Bean,Phaseolus vulgaris Lectin,Phaseolus vulgaris Lectins,Phytohemagglutinin,Hemagglutinins, Plant,Lectin, Kidney Bean,Lectin, Phaseolus vulgaris,Lectins, Phaseolus vulgaris,Plant Hemagglutinins
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003588	Cytopathogenic Effect, Viral	Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses.	Cytopathic Effect, Viral,Viral Cytopathogenic Effect,Cytopathic Effects, Viral,Cytopathogenic Effects, Viral,Effect, Viral Cytopathic,Effect, Viral Cytopathogenic,Effects, Viral Cytopathic,Effects, Viral Cytopathogenic,Viral Cytopathic Effect,Viral Cytopathic Effects,Viral Cytopathogenic Effects
D006377	T-Lymphocytes, Helper-Inducer	Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.	Helper Cell,Helper Cells,Helper T Cell,Helper-Inducer T-Lymphocytes,Inducer Cell,Inducer Cells,T-Cells, Helper-Inducer,T-Lymphocytes, Helper,T-Lymphocytes, Inducer,Helper T-Cells,Cell, Helper T,Cells, Helper T,Helper Inducer T Lymphocytes,Helper T Cells,Helper T-Cell,Helper T-Lymphocyte,Helper T-Lymphocytes,Helper-Inducer T-Cell,Helper-Inducer T-Cells,Helper-Inducer T-Lymphocyte,Inducer T-Lymphocyte,Inducer T-Lymphocytes,T Cell, Helper,T Cells, Helper,T Cells, Helper Inducer,T Lymphocytes, Helper,T Lymphocytes, Helper Inducer,T Lymphocytes, Inducer,T-Cell, Helper,T-Cell, Helper-Inducer,T-Cells, Helper,T-Lymphocyte, Helper,T-Lymphocyte, Helper-Inducer,T-Lymphocyte, Inducer
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man