? Platelets are abundant, anucleated cells that mediate multiple functions, the most readily recognized of which is coagulation and hemostasis. It is now clear that activated platelets modulate local inflammatory responses including contact sensitivity, inflammatory bowel disease, and atherosclerosis through the interaction of platelet-derived ligands with endothelial cells and infiltrating leukocytes. Also, platelets express CD40L (CD154), which is an important ligand for modulating adaptive immunity. To determine whether platelet-derived CD40L also modulated adaptive immunity, studies were initiated to characterize the effect of CD40L on T and B cell responses. A clear understanding of the platelet-derived signals necessary for optimal induction of adaptive immunity is important to understanding early events in immune activation. Data recently reported by our group demonstrate that platelet-derived CD40L is important for the development of adaptive immunity. The data demonstrate that activated platelets induce dendritic cell maturation and B cell isotype switching, and enhance CD8+ T cell responses. Importantly, platelet-derived CD40L alone was sufficient for the induction of isotype switching by B cells and augmentation of T lymphocyte antiviral responses. Furthermore, normal mice depleted of platelets prior to adenovirus injection exhibit decreased production of adenovirus-specific IgG, and platelets were shown to be necessary for enhanced B cell germinal center formation, underscoring the importance of platelets in the generation of an optimal adaptive immune response. We hypothesize that platelet-derived CD40L is an early signal from the innate immune compartment that is necessary for optimal development of adaptive immunity. To test the hypothesis, studies are outlined to assess the effect of platelet-derived CD40L on B cell activation and antibody production. ? LAY STATEMENT Several diseases including atherosclerosis, inflammatory bowel disease, and diabetes are believed to arise from improperly regulated inflammatory immune responses, of which platelets may play a significant role. Identifying and characterizing mechanisms of platelet modulation of the immune response will aid in treatment strategies for combating these clinical situations. ? ?
| Elzey, Bennett D; Ratliff, Timothy L; Sowa, Jennifer M et al. (2011) Platelet CD40L at the interface of adaptive immunity. Thromb Res 127:180-3 |
| Elzey, Bennett D; Schmidt, Nathan W; Crist, Scott A et al. (2008) Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge. Blood 111:3684-91 |
| Sprague, Daniel L; Elzey, Bennett D; Crist, Scott A et al. (2008) Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles. Blood 111:5028-36 |
