T-cells produce acidic niches in lymph nodes to suppress their own effector functions.
Animals
CD4-Positive T-Lymphocytes
/ metabolism
CD8-Positive T-Lymphocytes
/ metabolism
Cell Proliferation
/ genetics
Flow Cytometry
Hydrogen-Ion Concentration
Immunochemistry
Lymph Nodes
/ metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Monocarboxylic Acid Transporters
/ genetics
Phosphofructokinase-1
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 08 2020
17 08 2020
Historique:
received:
21
11
2019
accepted:
13
07
2020
entrez:
19
8
2020
pubmed:
19
8
2020
medline:
9
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32807791
doi: 10.1038/s41467-020-17756-7
pii: 10.1038/s41467-020-17756-7
pmc: PMC7431837
doi:
Substances chimiques
Monocarboxylic Acid Transporters
0
Phosphofructokinase-1
EC 2.7.1.11
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4113Subventions
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA239219
Pays : United States
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