Back to Search
Start Over
T-cells produce acidic niches in lymph nodes to suppress their own effector functions
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020), Nature Communications, Nat Commun
- Publication Year :
- 2020
- Publisher :
- Nature Portfolio, 2020.
-
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.<br />T-cell activation primarily occurs in the lymph nodes, highly organized and specialized secondary lymphoid organs. Here the authors show that the acidic extracellular pH in lymph node paracortical zones limits cytokine production by effector T-cells, but does not alter their activation by antigen-presenting cells.
- Subjects :
- 0301 basic medicine
CD4-Positive T-Lymphocytes
Male
Physiology
medicine.medical_treatment
Phosphofructokinase-1
General Physics and Astronomy
02 engineering and technology
CD8-Positive T-Lymphocytes
Mice
Glycolysis
lcsh:Science
Lymph node
Mice, Knockout
Mice, Inbred BALB C
Multidisciplinary
medicine.diagnostic_test
Chemistry
Effector
Immunochemistry
Hydrogen-Ion Concentration
021001 nanoscience & nanotechnology
Flow Cytometry
tumor, acidosis, pH imaging, MRI, CEST
pH imaging
Cell biology
medicine.anatomical_structure
Cytokine
acidosis
Lymph
0210 nano-technology
CEST
MRI
Monocarboxylic Acid Transporters
tumor
Science
Immunology
General Biochemistry, Genetics and Molecular Biology
Article
Flow cytometry
03 medical and health sciences
Immune system
medicine
Extracellular
Animals
Cell Proliferation
General Chemistry
Mice, Inbred C57BL
030104 developmental biology
lcsh:Q
Lymph Nodes
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....2df969201dbc11c0cce79f6d53626090