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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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Submitted May 23, 2007
Accepted February 1, 2008
Platelet-derived CD154 enables T-cell priming and protection against listeria monocytogenes challenge
Bennett D. Elzey*, Nathan W. Schmidt, Scott A. Crist, Timothy P. Kresowik, John T. Harty, Bernhard Nieswandt, and Timothy L. Ratliff
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, United States
Department of Microbiology, University of Iowa, Iowa City, IA, United States
Department of Urology, University of Iowa, Iowa City, IA, United States
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, United States
Rudolf Virchow Center, DFG Rsearch Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany
Purdue Cancer Center, Purdue University, West Lafayette, IN, United States
* Corresponding author; email: belzey{at}iupui.edu.
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 protective immunity to Listeria challenge. Specifically, we demonstrate that Ad5-mOVA delivered in collagen induces higher ovalbumin-specific cytotoxic T lymphocyte (CTL) activity in a dose-dependent manner compared to 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 chicken ovalbumin expression (Lm-OVA) whereas mice immunized with low-dose Ad5-mOVA in PBS were not. These data indicate that in a physiologic setting which 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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