Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge.
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.
Elzey
Bennett D
BD
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA. belzey@iupui.edu
Schmidt
Nathan W
NW
Crist
Scott A
SA
Kresowik
Timothy P
TP
Harty
John T
JT
Nieswandt
Bernhard
B
Ratliff
Timothy L
TL
D000256:Adenoviridae; D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology*; D003094:Collagen / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014945:Wound Healing / Q000235:genetics / Q000276:immunology
D011994:Recombinant Proteins; D023201:CD40 Ligand; D010047:Ovalbumin; D003094:Collagen