IntroductionAplasia and hematological malignancies are treated with platelet transfusions, which can have major immunomodulatory effects. Platelet concentrates (PCs) contain many immunomodulatory elements, including the platelets themselves, residual leukocytes, extracellular vesicles, such as microparticles (MPs), cytokines and other soluble elements. Two of these components, MPs and a soluble form of CD27 (sCD27), have been shown to play a particularly important role in immune system modulation. The loss of CD27 expression is an irreversible marker of terminal effector CD3+ T-lymphocyte (TL) differentiation, and the CD27+ MPs present in PCs may maintain CD27 expression on the surface of TLs, and, thus, the activation of these cells.MethodsIn this study, we phenotyped the CD27-expressing MPs present in PCs by microscale flow cytometry and investigated the interaction of these particles with CD4+ TLs. We cocultured MPs and PBMCs and determined the origin of the CD27 expressed on the surface of CD4+ TLs with the aid of two fluorochromes (BV510 for CD27 originating from MPs and BV786 for cellular CD27).ResultsWe showed that the binding of CD27- expressing MPs involved the CD70 molecule, which was also present on these MPs. Finally, the maintenance of CD27 expression on the surface of TLs by sorted CD27+ MPs led to activation levels lower than those observed with other types of MPs.DiscussionThese results for CD27-expressing MPs and their CD70-mediated targeting open up new possibilities for immunotherapy based on the use of MPs to maintain a phenotype or to target immune cells, for example. Moreover, decreasing the levels of CD27-expressing MPs in transfused platelets might also increase the chances of success for anti-CD27 monoclonal immunotherapy.

Extracellular vesicles (EVs), which are generated by cell membrane budding in diverse cells, are present in variable numbers in the blood. An immunoregulatory role has been demonstrated principally for heterologous EVs, but the function of the EVs present naturally in blood remains unknown. We hypothesize that these autologous EVs might also modulate the phenotype and function of immune system cells, especially CD4+ T lymphocytes (TLs), as previously described for heterologous EVs. Several membranes and soluble immunoregulatory molecules were studied after the treatment of CD4+ TLs with autologous EVs. No direct activation was detected with autologous EVs, contrasting with the findings for heterologous EVs. However, following treatment with autologous EVs, a soluble form of CD27 (sCD27) was detected. sCD27 is strongly associated with lymphoproliferation. Autologous EVs have been shown to increase TL proliferation only after T-cell receptor (TcR) engagement due to polyclonal or specific-antigen stimulation. Our results therefore suggest that the EVs present in the blood have an immunomodulatory role different from that of heterologous EVs. These findings should be taken into account in future studies, particularly those focusing on infectious diseases, autotransfusion or doping practices.