Dynamic regulation of IFN-gamma signaling in antigen-specific CD8+ T cells responding to infection.
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.
Haring
Jodie S
JS
Department of Microbiology, University of Iowa, Iowa City, 52242, USA.
Corbin
Gail A
GA
Harty
John T
JT
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000637:transplantation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D007108:Immune Tolerance; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007700:Kinetics; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494080:Stat1 protein, mouse