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

Longo D. L.;
2020-01-01

Abstract

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.
2020
Inglese
Esperti anonimi
11
1
1
13
13
https://www.nature.com/articles/s41467-020-17756-7.pdf
tumor, acidosis, pH imaging, MRI, CEST
STATI UNITI D'AMERICA
1 – prodotto con file in versione Open Access (allegherò il file al passo 6 - Carica)
262
19
Wu H.; Estrella V.; Beatty M.; Abrahams D.; El-Kenawi A.; Russell S.; Ibrahim-Hashim A.; Longo D.L.; Reshetnyak Y.K.; Moshnikova A.; Andreev O.A.; Lud...espandi
info:eu-repo/semantics/article
partially_open
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1863720
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