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Dynamic regulation of IFN-gamma signaling in antigen-specific CD8+ T cells responding to infection
Journal article   Peer reviewed

Dynamic regulation of IFN-gamma signaling in antigen-specific CD8+ T cells responding to infection

Jodie S Haring, Gail A Corbin and John T Harty
The Journal of immunology (1950), Vol.174(11), pp.6791-6802
06/01/2005
DOI: 10.4049/jimmunol.174.11.6791
PMID: 15905520

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Abstract

IFN-gamma plays a critical role in the CD8(+) T cell response to infection, but when and if this cytokine directly signals CD8(+) T cells during an immune response is unknown. We show that naive Ag-specific CD8(+) T cells receive IFN-gamma signals within 12 h after in vivo infection with Listeria monocytogenes and then become unresponsive to IFN-gamma throughout the ensuing Ag-driven expansion phase. Ag-specific CD8(+) T cells regain partial IFN-gamma responsiveness throughout the contraction phase, whereas the memory pool exhibits uniform, but reduced, responsiveness that is also modulated during the secondary response. The responsiveness of Ag-specific CD8(+) T cells to IFN-gamma correlated with modulation in the expression of IFN-gammaR2, but not with IFN-gammaR1 or suppressor of cytokine signaling-1. This dynamic regulation suggests that early IFN-gamma signals participate in regulation of the primary CD8(+) T cell response program, but that evading or minimizing IFN-gamma signals during expansion and the memory phase may contribute to appropriate regulation of the CD8(+) T cell response.
 Phosphorylation Intracellular Fluid - immunology CD8-Positive T-Lymphocytes - transplantation Interferon-gamma - metabolism Listeria monocytogenes - immunology Intracellular Fluid - microbiology DNA-Binding Proteins - metabolism Signal Transduction - immunology Immunization, Secondary Listeriosis - immunology CD8-Positive T-Lymphocytes - metabolism Receptors, Interferon - antagonists & inhibitors Intracellular Fluid - metabolism CD8-Positive T-Lymphocytes - microbiology Mice, Inbred C57BL Cells, Cultured Immune Tolerance Interferon-gamma - physiology Mice, Transgenic Mice, Knockout Animals Epitopes, T-Lymphocyte - physiology Down-Regulation - immunology STAT1 Transcription Factor Immunologic Memory Trans-Activators - metabolism Mice Kinetics CD8-Positive T-Lymphocytes - immunology Receptors, Interferon - biosynthesis

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