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 sub(2)-Chain Expression

• Published in: The Journal of immunology (1950) 2000-03, Vol.164 (6), p.3056-3064
• Main Authors: Yin, Zhinan, Zhang, Dong-Hong, Welte, T, Bahtiyar, G, Jung, Sungsoo, Liu, Lanzhen, Fu, Xin-Yuan, Ray, A, Craft, J
• Format: Article
• Language: English
• Subjects: g-Interferon; Interleukin 12 receptors
• ISSN: 0022-1767

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 super(+) 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 super(+) Th1 cells, IFN- gamma -producing cells expressed the IL-12 receptor beta sub(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.