T-cells produce acidic niches in lymph nodes to suppress their own effector functions

The acidic pH of tumors profoundly inhibits effector functions of activated CD8+ T-cells. This study hypothesizes that this is a physiological process in immune regulation, occurring within acidic lymph nodes (LNs) due to low convective flow and high glucose metabolism. In vivo imaging shows LN paracortical zones are acidic; these niches are absent in athymic and lymphodepleted mice, implicating T-cells in acidification. T-cell glycolysis is inhibited at low LN pH due to acid inhibition of monocarboxylate transporters (MCTs), creating negative feedback on glycolytic rate. This acidic pH, however, does not hinder initial naïve T-cell activation by dendritic cells. The study describes an acidic niche regulating T-cell activation within the immune system.

Hao Wu, Veronica Estrella, Matthew Beatty, Dominique Abrahams, Asmaa El-Kenawi, Shonagh Russell, Arig Ibrahim-Hashim, Dario Livio Longo, Yana K. Reshetnyak, Anna Moshnikova, Oleg A. Andreev, Kimberly Luddy, Mehdi Damaghi, Krithika Kodumudi, Smitha R. Pillai, Pedro Enriquez-Navas, Shari Pilon-Thomas, Pawel Swietach, Robert J. Gillies