Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 310058, Hangzhou, P.R. China.
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Turin, Italy.
Department of Physics, University of Rhode Island, Kingston, RI, 02881, USA.
References: Not available.
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. We hypothesize that this is a physiological process in immune regulation, and that it occurs within lymph nodes (LNs), which are likely acidic because of low convective flow and high glucose metabolism. Here we show by in vivo fluorescence and MR imaging, that LN paracortical zones are profoundly acidic. These acidic niches are absent in athymic Nu/Nu and lymphodepleted mice, implicating T-cells in the acidifying process. T-cell glycolysis is inhibited at the low pH observed in LNs. We show that this is due to acid inhibition of monocarboxylate transporters (MCTs), resulting in a negative feedback on glycolytic rate. Importantly, we demonstrate that this acid pH does not hinder initial activation of naïve T-cells by dendritic cells. Thus, we describe an acidic niche within the immune system, and demonstrate its physiological role in regulating T-cell activation.
T-cells produce acidic niches in lymph nodes to suppress their own effector functions
No results.
T-cells produce acidic niches in lymph nodes to suppress their own effector functions