| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Frick, Corina Belle, Réka Fischer, Marco Dimeloe, Sarah Loeliger, Jordan Hess, Christoph Mehling, Matthias Sauder, Ursula Tay, Savas Langenkamp, Anja Bantug, Glenn R. Develioglu, Leyla |
| Description |
Author Affiliation: Dimeloe S ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Mehling M ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Frick C ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Loeliger J ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Bantug GR ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Sauder U ( Microscopy Center, Biocenter, University of Basel, 4056 Basel, Switzerland); Fischer M ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Belle R ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Develioglu L ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland); Tay S ( Department of Biosystems Science and Engineering, Swiss Federal Institute of Technology in Zurich, 4058 Basel, Switzerland); Langenkamp A ( Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, 4070 Basel, Switzerland.); Hess C ( Immunobiology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland) |
| Abstract |
Effector memory (EM) CD4(+) T cells recirculate between normoxic blood and hypoxic tissues to screen for cognate Ag. How mitochondria of these cells, shuttling between normoxia and hypoxia, maintain bioenergetic efficiency and stably uphold antiapoptotic features is unknown. In this study, we found that human EM CD4(+) T cells had greater spare respiratory capacity (SRC) than did naive counterparts, which was immediately accessed under hypoxia. Consequently, hypoxic EM cells maintained ATP levels, survived and migrated better than did hypoxic naive cells, and hypoxia did not impair their capacity to produce IFN-γ. EM CD4(+) T cells also had more abundant cytosolic GAPDH and increased glycolytic reserve. In contrast to SRC, glycolytic reserve was not tapped under hypoxic conditions, and, under hypoxia, glucose metabolism contributed similarly to ATP production in naive and EM cells. However, both under normoxic and hypoxic conditions, glucose was critical for EM CD4(+) T cell survival. Mechanistically, in the absence of glycolysis, mitochondrial membrane potential (ΔΨm) of EM cells declined and intrinsic apoptosis was triggered. Restoring pyruvate levels, the end product of glycolysis, preserved ΔΨm and prevented apoptosis. Furthermore, reconstitution of reactive oxygen species (ROS), whose production depends on ΔΨm, also rescued viability, whereas scavenging mitochondrial ROS exacerbated apoptosis. Rapid access of SRC in hypoxia, linked with built-in, oxygen-resistant glycolytic reserve that functionally insulates ΔΨm and mitochondrial ROS production from oxygen tension changes, provides an immune-metabolic basis supporting survival, migration, and function of EM CD4(+) T cells in normoxic and hypoxic conditions. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
1 |
| Volume Number |
196 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2016-01-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Apoptosis Immunology Cd4-positive T-lymphocytes Metabolism Cell Hypoxia Glucose Mitochondria Cell Line Cell Movement Cell Survival Glyceraldehyde-3-phosphate Dehydrogenase (phosphorylating) Glycolysis Immunologic Memory Interferon-gamma Biosynthesis Membrane Potential, Mitochondrial Microfluidics Oxygen Pyruvic Acid Reactive Oxygen Species Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
