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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.

Original publication

DOI

10.1038/s41467-020-17756-7

Type

Journal article

Journal

Nat Commun

Publication Date

17/08/2020

Volume

11

Keywords

Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Flow Cytometry, Hydrogen-Ion Concentration, Immunochemistry, Lymph Nodes, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Monocarboxylic Acid Transporters, Phosphofructokinase-1