Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism
Ana Paletta
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorFacundo Di Diego García
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorAugusto Varese
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorFernando Erra Diaz
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorJulián García
División C, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorJuan Carlos Cisneros
Unidad de Terapia Intensiva, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorGuillermina Ludueña
Departamento de Medicina Interna, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina
Search for more papers by this authorIgnacio Mazzitelli
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorAndrea Pisarevsky
Departamento de Medicina Interna, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina
Search for more papers by this authorGonzalo Cabrerizo
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorÁlvaro López Malizia
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorAlejandra G. Rodriguez
Unidad de Terapia Intensiva, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorNicolás Lista
Unidad de Terapia Intensiva, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorYesica Longueira
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorJuan Sabatté
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorJorge Geffner
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorFederico Remes Lenicov
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorCorresponding Author
Ana Ceballos
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Correspondence
Ana Ceballos, INBIRS, Facultad de Medicina, Universidad de Buenos Aires C1121ABG, Ciudad de Buenos Aires, Argentina.
Emails: [email protected]; [email protected]
Search for more papers by this authorAna Paletta
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorFacundo Di Diego García
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorAugusto Varese
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorFernando Erra Diaz
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorJulián García
División C, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorJuan Carlos Cisneros
Unidad de Terapia Intensiva, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorGuillermina Ludueña
Departamento de Medicina Interna, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina
Search for more papers by this authorIgnacio Mazzitelli
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorAndrea Pisarevsky
Departamento de Medicina Interna, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina
Search for more papers by this authorGonzalo Cabrerizo
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorÁlvaro López Malizia
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorAlejandra G. Rodriguez
Unidad de Terapia Intensiva, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorNicolás Lista
Unidad de Terapia Intensiva, Hospital de Enfermedades Infecciosas Francisco Muñiz, Buenos Aires, Argentina
Search for more papers by this authorYesica Longueira
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorJuan Sabatté
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorJorge Geffner
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorFederico Remes Lenicov
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Search for more papers by this authorCorresponding Author
Ana Ceballos
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina
Correspondence
Ana Ceballos, INBIRS, Facultad de Medicina, Universidad de Buenos Aires C1121ABG, Ciudad de Buenos Aires, Argentina.
Emails: [email protected]; [email protected]
Search for more papers by this authorAna Paletta and Facundo Di Diego García contributed equally to this work.
Funding information: This work was supported by grants from the ‘Fondo Nacional para la Investigación Científica y Tecnológica (FONCyT)’ (PICT 2017–1038 and IP-COVID to Ana Ceballos) and the Universidad de Buenos Aires (20020170100573BA to A.C).
Summary
Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4+ T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T-cell dysfunction in COVID-19. We observed a high frequency of CD4+ T cell–platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID-19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)-α production by CD4+ T cells. In addition, interferon (IFN)-γ production was increased by platelets from HD but not from COVID-19 inpatients. A high expression of PD-L1 was found in platelets from COVID-19 patients to be inversely correlated with IFN-γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD-L1-blocking antibody significantly restored platelets’ ability to stimulate IFN-γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID-19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.
CONFLICT OF INTERESTS
All authors report no potential conflicts.
Supporting Information
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