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Massive interleukin‐12‐induced interferon‐γ production by interleukin‐15‐stimulated lamina propria lymphocytes followed by down‐regulation of the interleukin‐12 receptor
Author(s) -
Ebert Ellen C.,
Jabri Bana
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02796.x
Subject(s) - biology , lamina propria , cytokine , immune system , interleukin , receptor , stat protein , stat4 , immunology , microbiology and biotechnology , antigen , interleukin 15 , interleukin 2 , signal transduction , stat , stat3 , epithelium , biochemistry , genetics
Summary The intestinal mucosal immune response must differentiate between harmless foreign antigens and pathogens, a distinction that may depend upon changes in the cytokine milieu. A key cytokine in the adaptive immune response is interleukin‐12 (IL‐12), secreted by antigen‐presenting cells (APC) immediately after encounter with a pathogen. IL‐12 is important in the priming and polarization of naïve T cells. Here, we show that IL‐12 and IL‐15 direct human intestinal lamina propria lymphocytes (LPL) in the absence of T‐cell receptor engagement to secrete extremely high amounts of interferon‐γ (IFN‐γ), greater than with any other stimulus. The functional synergy of IL‐12 with IL‐15 surprisingly operates independently of signal transducer and activator of transcription 1 (STAT1), STAT3, STAT4, or STAT5 phosphorylation and occurs during transcription. Four‐colour immunofluorescence showed that IL‐12 receptor β1 is found on the CD4 + T cells expressing intracytoplasmic IFN‐γ. Importantly, IL‐12 receptors β1 and β2 are not up‐regulated by IL‐12, unlike findings using antigen‐specific T cells, and are lost over time. This study demonstrates the early and massive IFN‐γ response of LPL to IL‐12 and IL‐15, providing the tools to deal with a pathogen. The down‐regulation of IL‐12 receptors may curtail any excess damaging inflammation.