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The Journal of Immunology, 2005, 174: 6791-6802.
Copyright © 2005 by The American Association of Immunologists

Dynamic Regulation of IFN-{gamma} Signaling in Antigen-Specific CD8+ T Cells Responding to Infection1

Jodie S. Haring*, Gail A. Corbin* and John T. Harty2,*,{dagger}

* Department of Microbiology and {dagger} Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242

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-{gamma}R2, but not with IFN-{gamma}R1 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.




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