CD4+ T CELLS INDUCE PLATELET ACTIVATION THROUGH THE RELEASE OF EXTRACELLULAR VESICLES

ROMANIUK, ALBERTINA; DUETTE, GABRIEL; PEREYRA GERBER, PEHUEN; RUBIONE, JULIA; PEREZ, PAULA S.; ADAMCZYK, ALAN; OSTROWSKI, MATIAS

Mar del Plata

Congreso; LXIV Reunión anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

Atherosclerosis is an inflammatory and thrombotic disease. Bothplatelets and lymphocytes play important roles in atheroma plaquedevelopment. However, knowledge on the interaction betweenthese cells and its consequences is limited. Extracellular Vesicles(EVs) have emerged as a novel intercellular communication system.By carrying bioactive lipids, miRNAs and proteins they can modulatetarget cell functions. EV secretion is increased in diverse pathologies such as cancer, infections and atherosclerosis. Also, previousresults from our laboratory have shown that activated CD4+ T cells(Th1) produce more vesicles compared to resting T cells. Therefore,in this work, we studied platelet-lymphocyte interaction through EVs.First, we characterized EVs secreted by activated CD4+ T cells bydetection of canonical EV markers CD63 and CD81 by immunoblot.The EV-excluded endoplasmic reticulum (ER) marker calnexin was,as expected, present in cell lysates but not in EVs. EV visualization by electron microscopy revealed that EVs secreted by CD4+T cells had a spherical shape and a diameter that ranged from 50to 200 nm. Incubation of purified EVs (ultracentrifugation) with human washed platelets induced platelet hemostatic responses suchas αIIbβ3 integrin activation, platelet aggregation and degranulation(CD63 exposure) in an extracellular calcium-dependent manner.Furthermore, CD4+ T cell derived EVs also induced P-selectin exposure, suggesting a pro-inflammatory role for this interaction. Wealso tested EVs purified from plasma and from the human mammarycarcinoma cell line MCF-7 and did not observe platelet activation,suggesting a specific effect for CD4+ T cell derived EVs. In summary, we describe an alternative mechanism of leukocyte-plateletcross-talk mediated by EVs that is of potential relevance for theearliest aspects of inflammation and hemostatic cell responses. Alternatively, this process may also contribute to the exacerbation ofleukocyte activation, and intercellular adhesion and migration duringthe initial phases of vascular injury and the atherosclerotic disease.