The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability
Open accessAbstract
A characteristic of memory T (T M ) cells is their ability to mount faster and stronger responses to reinfection than naïve T (T N ) cells do in response to an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found that CD8 T M cells have more mitochondrial mass than CD8 T N cells and, that upon activation, the resulting secondary effector T (T E ) cells proliferate more quickly, produce more cytokines, and maintain greater ATP levels than primary effector T cells. We also found that after activation, T M cells increase oxidative phosphorylation and aerobic glycolysis and sustain this increase to a greater extent than T N cells, suggesting that greater mitochondrial mass in T M cells not only promotes oxidative capacity, but also glycolytic capacity. We show that mitochondrial ATP is essential for the rapid induction of glycolysis in response to activation and the initiation of proliferation of both T N and T M cells. We also found that fatty acid oxidation is needed for T M cells to rapidly respond upon restimulation. Finally, we show that dissociation of the glycolysis enzyme hexokinase from mitochondria impairs proliferation and blocks the rapid induction of glycolysis upon T-cell receptor stimulation in T M cells. Our results demonstrate that greater mitochondrial mass endows T M cells with a bioenergetic advantage that underlies their ability to rapidly recall in response to reinfection.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“We have recently shown that increased mitochondrial mass and SRC of TM cells allows for rapid mitochondrial ATP production upon TCR engagement, conferring a bioenergetic advantage to TM cells upon secondary exposure to antigen (16).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis
Chang, C.-H., Curtis, J. D., Maggi, L. B., Faubert, B., Villarino, A. V., O’Sullivan, D., Huang, S. C.-C., van der Windt, G. J. W., Blagih, J., Qiu, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.016 · Cited by 2,204
Self-citationLineage relationship and protective immunity of memory CD8 T cell subsets
Wherry, E. J., Teichgräber, V., Becker, T. C., Masopust, D., Kaech, S. M., Antia, R., von Andrian, U. H., & Ahmed, R. (2003) · Nature Immunology · doi:10.1038/ni889 · Cited by 1,864
Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
van der Windt, G. J. W., Everts, B., Chang, C.-H., Curtis, J. D., Freitas, T. C., Amiel, E., Pearce, E. J., & Pearce, E. L. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.007 · Cited by 1,540
Self-citationMolecular and functional profiling of memory CD8 T cell differentiation.
Kaech, S., Hemby, S., Kersh, E., & Ahmed, R. (2002) · Cell · doi:10.1016/s0092-8674(02)01139-x · Cited by 1,081
A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila , and Humans
Bricker, D. K., Taylor, E. B., Schell, J. C., Orsak, T., Boutron, A., Chen, Y.-C., Cox, J. E., Cardon, C. M., Van Vranken, J. G., Dephoure, N., et al. (2012) · Science · doi:10.1126/science.1218099 · Cited by 843
Fuel feeds function: energy metabolism and the T-cell response
Fox, C. J., Hammerman, P. S., & Thompson, C. B. (2005) · Nature reviews. Immunology · doi:10.1038/nri1710 · Cited by 841
Majewski, N., Nogueira, V., Bhaskar, P. T., Coy, P. E., Skeen, J. E., Gottlob, K., Chandel, N. S., Thompson, C. B., Robey, R. B., & Hay, N. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.11.014 · Cited by 638
Metabolic switching and fuel choice during T‐cell differentiation and memory development
van der Windt, G. J. W., & Pearce, E. L. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01150.x · Cited by 563
Self-citationResponse of naïve and memory CD8+ T cells to antigen stimulation in vivo
Veiga‐Fernandes, H., Walter, U., Bourgeois, C., McLean, A. R., & Rocha, B. (2000) · Nature Immunology · doi:10.1038/76907 · Cited by 547
Rathmell, J. C., Heiden, M. G. V., Harris, M. H., Frauwirth, K. A., & Thompson, C. B. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00066-6 · Cited by 467
Haluszczak, C., Akue, A., Hamilton, S. E., Johnson, L., Pujanauski, L., Teodorovic, L. S., Jameson, S., & Kedl, R. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081829 · Cited by 397
Revving the Engine: Signal Transduction Fuels T Cell Activation
Jones, R. G., & Thompson, C. B. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.008 · Cited by 349
Self-citationDeBerardinis, R. J., Lum, J. J., & Thompson, C. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608372200 · Cited by 221
Functional differences between memory and naive CD8 T cells
Cho, B. K., Wang, C., Sugawa, S., Eisen, H. N., & Chen, J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.2976 · Cited by 214
Differential Sensitivity of Naive and Memory CD8+ T Cells to Apoptosis in Vivo
Grayson, J. M., Harrington, L. E., Lanier, J. G., Wherry, E. J., & Ahmed, R. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.7.3760 · Cited by 211
Epigenetic Remodeling of the IL-2 and IFN -γ Loci in Memory CD8 T Cells Is Influenced by CD4 T Cells
Northrop, J. K., Thomas, R. M., Wells, A. D., & Shen, H. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.1062 · Cited by 203
Bioenergetic Profile Experiment using C2C12 Myoblast Cells
Nicholls, D. G., Darley-Usmar, V. M., Wu, M., Jensen, P. B., Rogers, G. W., & Ferrick, D. A. (2010) · Journal of Visualized Experiments · doi:10.3791/2511 · Cited by 198
Rapid Demethylation of the IFN-γ Gene Occurs in Memory but Not Naive CD8 T Cells
Kersh, E. N., Fitzpatrick, D. R., Murali‐Krishna, K., Shires, J., Speck, S. H., Boss, J. M., & Ahmed, R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.4083 · Cited by 189
Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes
Roos, D., & Loos, J. A. (1973) · Experimental Cell Research · doi:10.1016/0014-4827(73)90561-2 · Cited by 182
Cerwenka, A., Morgan, T., & Dutton, R. W. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.10.5535 · Cited by 170
Naive, Effector and Memory CD8 T-cell Trafficking: Parallels and Distinctions
Nolz, J. C., Starbeck-Miller, G. R., & Harty, J. T. (2011) · Immunotherapy · doi:10.2217/imt.11.100 · Cited by 162
Spare respiratory capacity, oxidative stress and excitotoxicity
Nicholls, D. G. (2009) · Biochemical Society Transactions · doi:10.1042/bst0371385 · Cited by 161
Carnitine acyltransferases and their influence on CoA pools in health and disease
RAMSAY, R. (2004) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2004.06.002 · Cited by 153
Signaling Takes a Breath – New Quantitative Perspectives on Bioenergetics and Signal Transduction
Krauss, S., Brand, M. D., & Buttgereit, F. (2001) · Immunity · doi:10.1016/s1074-7613(01)00205-9 · Cited by 147
Clotrimazole and bifonazole detach hexokinase from mitochondria of melanoma cells
Penso, J., & Beitner, R. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)01507-0 · Cited by 136
Requirements for CD8 T-cell priming, memory generation and maintenance
Prlic, M., Williams, M. A., & Bevan, M. J. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.04.010 · Cited by 135
A high-throughput respirometric assay for mitochondrial biogenesis and toxicity
Beeson, C. C., Beeson, G. C., & Schnellmann, R. G. (2010) · Analytical Biochemistry · doi:10.1016/j.ab.2010.04.040 · Cited by 134
TCR Signal Transduction in Antigen-Specific Memory CD8 T Cells
Kersh, E. N., Kaech, S. M., Onami, T. M., Moran, M., Wherry, E. J., Miceli, M. C., & Ahmed, R. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.11.5455 · Cited by 112
Loos, J. A., & Roos, D. (1973) · PubMed · Cited by 107
Carrió, R., Bathe, O. F., & Malek, T. R. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7315 · Cited by 102
Targeting of hexokinase 1 to liver and hepatoma mitochondria.
Gelb, B. D., Adams, V., Jones, S. N., Griffin, L. D., MacGregor, G. R., & McCabe, E. R. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.1.202 · Cited by 95
Northrop, J. K., Wells, A. D., & Shen, H. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.2.865 · Cited by 89
César, M. C., & Wilson, J. E. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0497 · Cited by 73
Biochemical signaling pathways for memory T cell recall
Färber, D. L. (2009) · Seminars in Immunology · doi:10.1016/j.smim.2009.02.003 · Cited by 68
Population Dynamics of Naive and Memory CD8 T Cell Responses after Antigen Stimulations In Vivo
Martin, M. D., Condotta, S. A., Harty, J. T., & Badovinac, V. P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101579 · Cited by 55
Quick to remember, slow to forget: rapid recall responses of memory CD8+ T cells
DiSpirito, J. R., & Shen, H. (2009) · Cell Research · doi:10.1038/cr.2009.140 · Cited by 51
Interaction of mitochondrial porin with cytosolic proteins
Brdiczka, D. G. (1990) · Cellular and Molecular Life Sciences · doi:10.1007/bf02027312 · Cited by 44
BeltrandelRio, H., & Wilson, J. E. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90252-r · Cited by 41
Nederlof, R., Xie, C., Eerbeek, O., Koeman, A., Milstein, D. M. J., Hollmann, M. W., Mik, E. G., Warley, A., Southworth, R., Akar, F. G., et al. (2013) · Circulation Research · doi:10.1161/circresaha.112.274308 · Cited by 13
Cited by
Sorted by citations
A guide to immunometabolism for immunologists
O'Neill, L. A. J., Kishton, R. J., & Rathmell, J. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.70 · Cited by 3,315
Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming
Buck, M. D., O’Sullivan, D., Geltink, R. I. K., Curtis, J. D., Chang, C., Sanin, D. E., Qiu, J., Kretz, O., Braas, D., van der Windt, G. J. W., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.035 · Cited by 1,491
Self-citationFueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363
Self-citationThommen, D. S., & Schumacher, T. N. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.012 · Cited by 1,351
Homeostatic Immunity and the Microbiota
Belkaid, Y., & Harrison, O. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.008 · Cited by 1,261
Metadata
- Authors
- van der Windt, G. J. W., O’Sullivan, D., Everts, B., Huang, S. C.-C., Buck, M. D., Curtis, J. D., Chang, C.-H., Smith, A. M., Ai, T., Faubert, B., Jones, R. G., Pearce, E. J., & Pearce, E. L.
- Affiliations
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; and
- Washington University in St. Louis (US)
- McGill University (CA)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-12
- Volume
- 110
- Issue
- 35
- Pages
- 14336-14341
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3761631
- OpenAlex
- W2061318708
- Cited by
- 523
- References
- 39
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 27 · 2023: 40 · 2022: 50 · 2021: 54 · 2020: 55 · 2019: 56 · 2018: 44 · 2017: 46 · 2016: 44 · 2015: 30 · 2014: 19 · 2013: 2
- FWCI
- 17.50
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (R01CA164062)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- memory CD8+ T cells, mitochondrial mass, recall response, oxidative phosphorylation, aerobic glycolysis, fatty acid oxidation, hexokinase, mitochondrial ATP, T cell proliferation, T cell receptor stimulation, cytokine production
- MeSH terms
- Animals, Energy Metabolism, Immunologic Memory, Lymphocyte Activation, CD8-Positive T-Lymphocytes, Mice, Mitochondrial Size
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
