Evidence of positive cross-regulation on Th1 by Th2 and antigen-presenting cells: effects on Th1 induced by IL-4 and IL-12. 1999

T B Oriss, and S A McCarthy, and M A Campana, and P A Morel
University of Pittsburgh Cancer Institute, Department of Medicine, PA 15213, USA.

The response of Th cells to cytokines is normally strictly regulated, such that following antigenic stimulation, Th cells respond for only a short period of time, after which they become refractory to cytokine-mediated effects. IL-12, a costimulator of Th1 having no proliferation-inducing capacity of its own, allows Th1 clones and lines to respond to IL-4 when they would otherwise be unable to respond to this cytokine. Cells that have proliferated in response to IL-4 plus IL-12 are fully able to be subsequently activated by specific Ag and APC. Additionally, the response to IL-4 of Th1 effector cells derived from normal murine spleen is enhanced significantly by IL-12. Furthermore, in the presence of IL-12, stimulated Th2 can induce proliferation of Th1 via IL-4 production, in a dual chamber culture system. We hypothesize that the effects of IL-4 and IL-12 represent a novel, positive cross-regulatory pathway that acts on Th1, and is mediated by Th2 (the IL-4 source) and APC (the IL-12 source). We propose this as a way for a Th2 immune response to positively influence an ongoing or waning Th1 response.

UI MeSH Term Description Entries
D007399 Interphase The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs). Interphases
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
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002469 Cell Separation Techniques for separating distinct populations of cells. Cell Isolation,Cell Segregation,Isolation, Cell,Cell Isolations,Cell Segregations,Cell Separations,Isolations, Cell,Segregation, Cell,Segregations, Cell,Separation, Cell,Separations, Cell
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
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005260 Female Females

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