Presenting Author: Gisele V Baracho
, Staff Scientist at BD BioSci.
Abstract:
Upon activation, T cells undergo metabolic adaptations to fulfill the energy and biosynthetic requirements for their rapid growth and proliferation. TCR engagement and CD28 co-stimulation trigger the initial metabolic shifts that enable T-cell activation including increased glucose uptake. PI3K signaling plays a pivotal role in regulating Glut-1, the primary glucose transporter in T cells. Using high-dimensional spectral flow cytometry, we found correlated expression between Glut-1 and granzyme B (GZMB) in subsets of in vitro-activated human T cells. Notably, the PI3K inhibitor Ly294002 abrogated TCR-dependent upregulation of Glut-1 abolishing Glut-1highGZMB+ T cells in the cultures. A comprehensive single-cell targeted mRNA profiling of over 56, 000 immune cells captured with the BD Rhapsody™ HT Xpress System further showed a TCR-dependent upregulation of GZMB and various metabolic regulators such as GAPDH, HMGB2 and TK1. The results provide additional details on the involvement of the glycolytic pathway in T cell activation and offer a deeper insight into the molecular mechanisms associated with TCR-dependent cell activation.