Dominance of IL-12 over IL-4 in gamma delta T cell differentiation leads to default production of IFN-gamma: failure to down-regulate IL-12 receptor beta 2-chain expression.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Dominance of IL-12 over IL-4 in gamma delta T cell differentiation leads to default production of IFN-gamma: failure to down-regulate IL-12 receptor beta 2-chain expression.

J Immunol. 2000 Mar 15;164(6):3056-64. Unique Identifier : AIDSLINE MED/20171504
Yin Z; Zhang DH; Welte T; Bahtiyar G; Jung S; Liu L; Fu XY; Ray A; Craft J; Sections of Rheumatology and Pulmonary and Critical Care; Medicine, Department of Medicine, Department of Pathology, and; Section of Immunobiology, Yale School of Medicine, New Haven, CT; 06520, USA.

Abstract: Gamma delta T cells secrete Th1- and Th2-like cytokines that help mediate innate and acquired immunity. We have addressed the mechanism whereby murine gamma delta T cells acquire the capacity to differentially produce such cytokines. Splenic gamma delta T cells could be polarized into IFN-gamma- or IL-4-secreting cells in vitro; however, in contrast to CD4+ alpha beta T cells, gamma delta T cells predominantly produced IFN-gamma, even in the presence of IL-4, a finding independent of genetic background. Like CD4+ Th1 cells, IFN-gamma-producing cells expressed the IL-12 receptor beta 2-chain after activation in the presence of IL-12; however, unlike Th2 cells, IL-4-primed gamma delta T cells also expressed this receptor, even in the absence of IFN-gamma and despite the presence of the transcription factor GATA-3. IL-12 also induced IL-4-primed gamma delta T cells to proliferate and to translocate Stat3/Stat4, indicating signaling through the IL-12 receptor. These molecular events can account for the predominant production of IFN-gamma by gamma delta T cells in the presence of IL-12, despite the availability of IL-4. Early and predominant production of IFN-gamma by gamma delta T cells likely is critical for the roles that these cells play in protection against intracellular pathogens and in tumor immunity.

Keywords: JOURNAL ARTICLE Animal Cell Differentiation/IMMUNOLOGY Cells, Cultured Cytokines/BIOSYNTHESIS Down-Regulation (Physiology)/*IMMUNOLOGY DNA-Binding Proteins/PHYSIOLOGY Interferon Type II/*BIOSYNTHESIS/SECRETION Interleukin-12/METABOLISM/*PHYSIOLOGY Interleukin-4/BIOSYNTHESIS/*PHYSIOLOGY Lymphocyte Transformation Mice Mice, Inbred BALB C Mice, Inbred C57BL Receptors, Antigen, T-Cell, gamma-delta/*METABOLISM Receptors, Interleukin/ANTAGONISTS & INHIB/*BIOSYNTHESIS Signal Transduction/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocyte Subsets/CYTOLOGY/*IMMUNOLOGY/*METABOLISM/SECRETION Th1 Cells/IMMUNOLOGY/METABOLISM Th2 Cells/IMMUNOLOGY/METABOLISM Trans-Activators/PHYSIOLOGY

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