CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program

CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4(+) effector memory T cells (T(EMs)) in humans with unwanted serious adverse effects. It is well known that distinct metabolic programs determine the fate and responses of...

Descripción completa

Detalles Bibliográficos
Autores principales: Thaventhiran, Thilipan, Wong, Wai, Alghanem, Ahmad F., Alhumeed, Naif, Aljasir, Mohammad A., Ramsey, Simeon, Sethu, Swaminathan, Yeang, Han Xian Aw, Chadwick, Amy E., Cross, Michael, Webb, Steven D., Djouhri, Laiche, Ball, Christina, Stebbings, Richard, Sathish, Jean G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634261/
https://www.ncbi.nlm.nih.gov/pubmed/31009338
http://dx.doi.org/10.1089/mab.2018.0042
Descripción
Sumario:CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4(+) effector memory T cells (T(EMs)) in humans with unwanted serious adverse effects. It is well known that distinct metabolic programs determine the fate and responses of immune cells. In this study, we show that human CD4(+) T(EMs) stimulated with CD28SA adopt a metabolic program similar to those of tumor cells with enhanced glucose utilization, lipid biosynthesis, and proliferation in hypoxic conditions. Identification of metabolic profiles underlying hyperactive T cell activation would provide a platform to test safety of immunostimulatory antibodies.

Ejemplares similares