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- Douglas V. Dolfi
- *Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129; and
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- Alina C. Boesteanu
- *Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129; and
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- Constantinos Petrovas
- *Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129; and
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- Dong Xia
- †Inflammation Department, Amgen, Seattle, WA 98119
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- Eric A. Butz
- †Inflammation Department, Amgen, Seattle, WA 98119
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- Peter D. Katsikis
- *Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129; and
説明
<jats:title>Abstract</jats:title> <jats:p>The role of costimulation has previously been confined to the very early stages of the CD8+ T cell response. In this study, we demonstrate the requirement for CD27 costimulation during the later phase, but not programming of the primary CD8+ T cell response to influenza virus and reveal a novel mechanism of action for CD27 costimulation. CD27 signals, during the later phase of the primary CD8+ T cell response, prevent apoptosis of Ag-specific CD8+ T cells. Blocking CD27L (CD70) on days 6 and 8 after infection reduces the number of NP(366–374)-specific CD8+ T cells, increases their sensitivity to CD95/Fas-mediated apoptosis, and up-regulates FasL on CD4+ T cells. This reduction of NP(366–374)-specific CD8+ T cells requires the presence of CD4+ T cells and Fas signaling. Lack of CD27 signals also decreases the quality of memory CD8+ T cell responses. Memory CD8+ T cells, which express surface CD27 similar to naive cells, however, do not require CD27 costimulation during a secondary response. Thus, CD27 acts indirectly to regulate primary Ag-specific CD8+ T cell responses by preventing apoptosis of CD8+ T cells during the later phase of the primary response and is required for optimal quality of memory cells, but is not required during normally primed secondary CD8+ T cell responses.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 180 (5), 2912-2921, 2008-03-01
The American Association of Immunologists