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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3684-3691.
Prepublished online as a Blood First Edition Paper on February 6, 2008; DOI 10.1182/blood-2007-05-091728.


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IMMUNOBIOLOGY

Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge

Bennett D. Elzey1,2, Nathan W. Schmidt3, Scott A. Crist1, Timothy P. Kresowik4, John T. Harty3,5, Bernhard Nieswandt6,7, and Timothy L. Ratliff1,8

1 Department of Comparative Pathobiology, Purdue University, West Lafayette, IN; 2 Department of Urology, Indiana University, Indianapolis; 3 Department of Microbiology, 4 Department of Urology, and 5 Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City; 6 Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, and 7 Institute of Clinical Biochemistry and Pathobiochemistry, University of Wurzburg, Wurzburg, Germany; and 8 Purdue Cancer Center, Purdue University, West Lafayette, IN

Collagen exposure in tissue activates platelets, initiates wound healing, and modulates adaptive immunity. In this report, data are presented to demonstrate a requirement for platelet-derived CD154 for both collagen-induced augmentation of T-cell immunity and induction of pro-tective immunity to Listeria challenge. Specifically, we demonstrate that Ad5 encoding the membrane-bound form of ovalbumin (Ad5-mOVA) delivered in collagen induces higher ovalbumin-specific cytotoxic T lymphocyte (CTL) activity in a dose-dependent manner compared with Ad5-mOVA delivered in PBS. Increased CTL activity was dependent on the ability of platelets to respond to collagen and to express CD154. Furthermore, mice immunized with low-dose Ad5-mOVA in collagen were able to control a challenge of Listeria monocytogenes recombinant for ovalbumin expression (Lm-OVA), whereas mice immunized with low-dose Ad5-mOVA in PBS were not. These data indicate that in a physiologic setting that mimics wounding, platelets perform a sentinel function when antigen dose is too low to provoke an efficient immune response, and can enhance the generation of antigen-specific CD8 T cells that are functionally relevant to the host.


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