Cutting edge: T cells trigger CD40-dependent platelet activation and granular RANTES release: a novel pathway for immune response amplification.
Platelets, in addition to exerting hemostatic activity, contribute to immunity and inflammation. The recent report that platelets express CD40 led us to hypothesize that CD40 ligand (CD40L)-positive T cells could bind to platelets, cause their activation, and trigger granular RANTES release, creating a T cell recruitment feedback loop. Platelets were cocultured with resting or activated autologous T cells and their activation was assessed by P-selectin expression. RANTES binding to endothelial cells was assessed by confocal microscopy, and its biological activity was demonstrated by a T cell adhesion assay. CD40L-positive T cells induced platelet activation through a contact-mediated, CD40-dependent pathway resulting in RANTES release, which bound to endothelial cells and mediated T cell recruitment. Soluble CD40L induced the same events via p38, but not extracellular signal-regulated kinase, phosphorylation. These results show the existence of a novel platelet-dependent pathway of immune response amplification which brings these nonimmune cells close to the level of pathogenic relevance traditionally attributed to classical immune cells.
Danese
Silvio
S
Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
de la Motte
Carol
C
Reyes
Brenda M Rivera
BM
Sans
Miquel
M
Levine
Alan D
AD
Fiocchi
Claudio
C
D000276:Adjuvants, Immunologic / Q000502:physiology; D001792:Blood Platelets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis / Q000502:physiology*; D023201:CD40 Ligand / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism* / Q000502:physiology; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000276:immunology* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D015539:Platelet Activation / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D018946:Chemokine CCL5; D023201:CD40 Ligand; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases