Platelet-associated CD154 in immune thrombocytopenic purpura

Solanilla, A.; Pasquet, Jean‐Max; Viallard, Jean‐François; Contin, Cécile; Grosset, Christophe; Déchanet‐Merville, Julie; Dupouy, Maryse; Landry, Marc; Belloc, Françis; Nurden, Paquita; Blanco, Patrick; Moreau, Jean-François; Pellegrin, Jean‐Luc; Ripoche, Jean

doi:10.1182/blood-2003-07-2367

Cited by 98 publications

(69 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…18 Others have shown that human platelets from immune thrombocytopenic purpura patients can directly stimulate autologous B cells to produce antiplatelet antibodies in vitro. 41 In addition to direct stimulation of B cells, platelets, through direct contact with T cells, release RANTES, creating a feedback loop for T-cell response amplification. 42 Furthermore, adoptively transferred human platelets via CD154 have been shown to cause immune-mediated rejection of allografts in mice.…”

Section: Discussionmentioning

confidence: 99%

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

Elzey

Schmidt

Crist

et al. 2008

Blood

View full text Add to dashboard Cite

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 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. IntroductionBecause pathogens are capable of logarithmic expansion upon host infection, it is critical that both innate and adaptive immunity are initiated without delay to ensure survival. An effective adaptive response is dependent upon efficient activation of innate immunity since antigen presenting cells (APCs) that are not fully activated are poor stimulators of T-or B-cell responses. [1][2][3] However, the initial infection usually involves entry of only a few microbes resulting in a very low antigen dose unlikely to provoke a prompt immune response. To compensate, the immune system has been designed with important activating early signaling components such as the Toll-like receptor (TLR) family, and costimulatory molecules such as CD40 ligand (CD40L, CD154), which help lower the threshold for cellular activation. 4,5 CD154 is a molecule critical to adaptive immunity. It is required for T-dependent humoral responses including affinity maturation, somatic hypermutation, germinal center (GC) formation, and B-cell memory. 6 In addition, there is a role in some models for CD154 in generation of normal CD8 T-cell memory and cross-presentation of class I-restricted antigen. [7][8][9][10][11][12][13] Until recently, functionally relevant expression of CD154 was thought to be restricted to CD4 T cells where its purpose in cellular immunity is to stimulate APCs that in turn potently activate T cells 2 ; however, functional CD154, which was able to generate an inflammatory response from endothelial cells, has also been reported on platelets. 14 The role platelets can play in antimicrobial immunity is well documented. They are activated by and able to engulf bacteria and viruses, release antimicrobial and antifungal proteins, release reactive oxygen species, express TLR, protect against helminth infections, and play a role in modulating ...

show abstract

Section: Discussionmentioning

confidence: 99%

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

Elzey

Schmidt

Crist

et al. 2008

Blood

View full text Add to dashboard Cite

show abstract

“…In vitro, le CD154 plaquettaire est capable d'activer les cellules dendritiques et d'induire la prolifération des lymphocytes B naïfs [15,31]. Ces données sont renforcées par la démonstration in vivo, dans des modèles murins, du rôle du CD154 plaquettaire dans la réponse immunitaire contre des virus [32].…”

Section: Compétence Immunologique Du Cd154 Plaquettaireunclassified

“…Cette maladie se caractérise par la présence d'auto-anticorps ciblant des déterminants antigé-niques présents sur les plaquettes, essentiellement la glycoprotéine GPIIb/IIIa, et responsables d'une destruction accélérée des plaquettes dans la rate et le foie. La capacité du CD154 plaquettaire à stimuler la prolifération des lymphocytes B et la différenciation des lymphocytes B autoréactifs dans le PTI a permis de suggérer l'implication du CD154 dans le processus d'auto-immunisation [15].…”

Section: Auto-immunitéunclassified

Le CD154 plaquettaire : Une nouvelle interface dans l’hémostase et la réaction inflammatoire

et al. 2005

Self Cite

View full text Add to dashboard Cite

Les plaquettes sanguines sont des éléments figurés du sang provenant de la fragmentation du cytoplasme des mégacaryocytes spécialisés dans la formation du clou hémostatique conduisant à l'arrêt du saignement [1][2][3]. La place de la plaquette dans la réaction inflammatoire a fait l'objet de très nombreux travaux que l'on pourrait schématiser en deux axes, l'un reflétant la participation directe des médiateurs pro-inflammatoires stockés dans les plaquettes et libérés lors de leur activation, l'autre les liens indirects entre activation plaquettaire et réaction inflammatoire, via le système du complément, la cascade des kinines, etc. Différen-tes revues ont été publiées concernant plaquettes et réaction inflammatoire, auxquelles nous renvoyons le lecteur [4]. La mise en évidence récente de l'expression du CD154 par les plaquettes a repositionné ces derniè-res dans la coagulation, la réaction inflammatoire et la réponse immunitaire. CD154 : une molécule indispensable à l'activation des lymphocytes BLe couple CD154/CD40 Le CD154 est une glycoprotéine membranaire de 30 kDa à 33 kDa présentant des homologies de séquence avec les molécules de la famille du tumor necrosis factor (TNF). Les protéines membranaires de cette famille sont > Il a récemment été montré que les plaquettes sanguines exprimaient le CD154 (ligand du CD40), qu'elles extériorisent à leur surface lors de leur activation. Cette découverte a eu des consé-quences importantes sur la compréhension de la biologie de la plaquette. D'une part, le CD154 intervient dans la stabilisation du thrombus plaquettaire. D'autre part, l'interaction des plaquettes avec les cellules exprimant le récepteur CD40 a mis en évidence de nouvelles interfaces liant les plaquettes à la réaction inflammatoire, la coagulation et le remodelage de la matrice extracellulaire. Cela est tout particulièrement vrai pour les interactions plaquettes/vaisseaux et le CD154 plaquettaire joue un rôle clé dans la maladie athéromateuse. Enfin, l'expression du CD154 confère aux plaquettes une compé-tence immunologique, leur faisant jouer un rôle potentiel dans la réponse immune ou dans les pathologies associées à une auto-immunisation antiplaquettaire comme le purpura thrombopé-nique idiopathique. Article disponible sur le site

show abstract

“…a more active role in the autoimmune process than simply bearing antigens and accepting a fate of destruction. 28 A number of investigators have studied the pattern of cytokine production in ITP. While there are conflicting results, most reports favor the interpretation that adult chronic ITP represents a predominantly Th1 type immune response characterized by production of interleukin-2 (IL-2) and interferon-γ (IFNγ).…”

Section: Emergence Of Antiplatelet Antibodiesmentioning

confidence: 99%

ITP in the 21st Century

Beardsley¹

2006

Hematology

View full text Add to dashboard Cite

Ten years ago the American Society of Hematology published immune (or idiopathic) thrombocytopenic purpura (ITP) practice guidelines based upon a systematic and comprehensive review of the literature.1 The authors acknowledged that hematologists regularly faced clinical management decisions with too little published scientific information about the natural history of ITP. Many of the treatments employed in ITP had been discovered empirically, and therapeutic choices were often guided by published results in case series of selected patients without a control group. Today, a decade later, we benefit from work by many investigators addressing the natural history of ITP and the pathogenic mechanisms contributing to autoimmune platelet destruction. Practice guidelines and a number of expert and consensus opinions in the literature have better defined the field.2-6 The recent era has also brought reports of new prospective clinical trials including multicenter, randomized studies that promise better guidance for the clinical hematologist in the 21st century. Recent clinical investigations of ITP assess outcome measures in addition to platelet count increments including quality of life, 7 severity of bleeding, 8 and complications of therapy. In addition, there are published reports of systematic analyses that help interpret previous literature. Hypothesis-driven studies of ITP patients and experimental animal models have also improved our understanding of the basic cellular and molecular immune mechanisms that contribute to ITP and have thus revealed new therapeutic opportunities.The present contribution will cover some of the recent basic research that has advanced our understanding of the pathogenesis of ITP and will highlight some of the clinical trials that offer insights into the diagnosis, natural history, and management of ITP in adults and children. Promising new therapeutic modalities for chronic refractory ITP will be discussed. Emphasis is placed upon explicitly designed trials. Several important clinical topics could not be included: secondary ITP, immune thrombocytopenia in pregnancy and infancy, the role of viral infection in ITP, and drug-related thrombocytopenia. Space limitations and edi-

show abstract

Platelet-associated CD154 in immune thrombocytopenic purpura

Cited by 98 publications

References 22 publications

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

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

Le CD154 plaquettaire : Une nouvelle interface dans l’hémostase et la réaction inflammatoire

ITP in the 21st Century

Contact Info

Product

Resources

About