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Late Signals from CD27 Prevent Fas-Dependent Apoptosis of Primary CD8⁺ T Cells¹

Douglas V. Dolfi^*, Alina C. Boesteanu^*, Constantinos Petrovas^*, Dong Xia, Eric A. Butz and Peter D. Katsikis^2,*

^* Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129; and Inflammation Department, Amgen, Seattle, WA 98119

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant R01 AI66215 (P.D.K.).

² Address correspondence and reprint requests to Dr. Peter D. Katsikis, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129. E-mail address: peter.katsikis{at}drexelmed.edu

³ Abbreviations used in this paper: DC, dendritic cell; i.n., intranasal; NP, nuclear protein; AICD, activation-induced cell death.

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The JI 2008 180: 2721-2722. [Full Text]  

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