Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism

PALETTA, ANA; DI DIEGO GARCÍA, FACUNDO; VARESE, AUGUSTO; ERRA DIAZ, FERNANDO; GARCÍA, JULIÁN; CISNEROS, JUAN CARLOS; LUDUEÑA, GUILLERMINA; MAZZITELLI, IGNACIO; PISAREVSKY, ANDREA; CABRERIZO, GONZALO; LÓPEZ MALIZIA, ÁLVARO; RODRIGUEZ, ALEJANDRA G.; LISTA, NICOLÁS; LONGUEIRA, YESICA; SABATTÉ, JUAN; GEFFNER, JORGE; REMES LENICOV, FEDERICO; CEBALLOS, ANA

BRITISH JOURNAL OF HAEMATOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2022 vol. 197 p. 283 - 292

0007-1048

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.