Peroxiredoxin II Regulates Effector and Secondary Memory CD8+T Cell Responses
Open accessAbstract
Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in cellular responses. However, the effect of increased H 2 O 2 on an antigen-specific CD8+T cell response was unknown. Following T cell receptor (TCR) stimulation, the expression and oxidation of peroxiredoxin II (PrdxII), a critical antioxidant enzyme, increased in CD8+T cells. Deletion of PrdxII increased ROI, S phase entry, division, and death during in vitro division. During primary acute viral and bacterial infection, the number of effector CD8+T cells in PrdxII-deficient mice was increased, while the number of memory cells were similar to those of the wild-type cells. Adoptive transfer of P14 TCR transgenic cells demonstrated that the increased expansion of effector cells was T cell autonomous. After rechallenge, effector CD8+T cells in mutant animals were more skewed to memory phenotype than cells from wild-type mice, resulting in a larger secondary memory CD8+T cell pool. During chronic viral infection, increased antigen-specific CD8+T cells accumulated in the spleens of PrdxII mutant mice, causing mortality. These results demonstrate that PrdxII controls effector CD8+T cell expansion, secondary memory generation, and immunopathology.
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If antioxidant molecules are depleted in T cells, cytokine production can become uncontrolled, potentially resulting in an inflammatory environment that is known to reactivate CMV.
“Finally, if antioxidant molecules are depleted in T cells, then cytokine production, can become uncontrolled (Michalek et al. 2012), potentially resulting in an inflammatory environment that is also known to reactivate CMV (Docke et al. 1994; Prosch et al. 1995; Stein et al. 1993).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Michalek et al. 2012
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Cites
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · see citing works
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 3,960 · see citing works
Bcl-2 functions in an antioxidant pathway to prevent apoptosis
Hockenbery, D. M., Oltvai, Z. N., Yin, X., Milliman, C. L., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)80066-n · Cited by 3,420 · see citing works
Structure, mechanism and regulation of peroxiredoxins
Wood, Z. A., Schröder, E., Harris, J. R., & Poole, L. B. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)00003-8 · Cited by 2,546 · see citing works
Self-citationBlackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062 · see citing works
Counting Antigen-Specific CD8 T Cells: A Reevaluation of Bystander Activation during Viral Infection
Murali‐Krishna, K., Altman, J. D., Suresh, M., Sourdive, D. J. D., Zajac, A. J., Miller, J. D., Slansky, J. E., & Ahmed, R. (1998) · Immunity · doi:10.1016/s1074-7613(00)80470-7 · Cited by 1,918 · see citing works
Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.010 · Cited by 1,861 · see citing works
Redox Regulation of Fos and Jun DNA-Binding Activity in Vitro
Abate, C., Patel, L., Rauscher, F. J., & Curran, T. (1990) · Science · doi:10.1126/science.2118682 · Cited by 1,573 · see citing works
Enhancing CD8 T-cell memory by modulating fatty acid metabolism
Pearce, E. L., Walsh, M. C., Cejas, P. J., Harms, G. M., Shen, H., Wang, L.-S., Jones, R. G., & Choi, Y. (2009) · Nature · doi:10.1038/nature08097 · Cited by 1,559 · see citing works
Peroxiredoxin Evolution and the Regulation of Hydrogen Peroxide Signaling
Wood, Z. A., Poole, L. B., & Karplus, P. A. (2003) · Science · doi:10.1126/science.1080405 · Cited by 1,369 · see citing works
Self-citationEffector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
Intlekofer, A. M., Takemoto, N., Wherry, E. J., Longworth, S. A., Northrup, J. T., Palanivel, V., Mullen, A. C., Gasink, C. R., Kaech, S. M., Miller, J. D., et al. (2005) · Nature Immunology · doi:10.1038/ni1268 · Cited by 1,257 · see citing works
CD8+ T Cells: Foot Soldiers of the Immune System
Zhang, N., & Bevan, M. J. (2011) · Immunity · doi:10.1016/j.immuni.2011.07.010 · Cited by 1,102 · see citing works
Kusmartsev, S. A., Nefedova, Y., Yoder, D., & Gabrilovich, D. I. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.2.989 · Cited by 851 · see citing works
Matthews, J. R., Wakasugi, N., Virelizier, J., Yodoi, J., & Hay, R. T. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.15.3821 · Cited by 831 · see citing works
Ahmed, R., Salmi, A. A., Butler, L. D., Chiller, J. M., & Oldstone, M. B. A. (1984) · The Journal of Experimental Medicine · doi:10.1084/jem.160.2.521 · Cited by 792 · see citing works
Xanthoudakis, S., & Curran, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05097.x · Cited by 708 · see citing works
Rutishauser, R. L., Martins, G. A., Kalachikov, S. M., Chandele, A., Parish, I. A., Meffre, E., Jacob, J., Calame, K. L., & Kaech, S. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.014 · Cited by 612 · see citing works
Cutting Edge: Naive T Cells Masquerading as Memory Cells
Murali‐Krishna, K., & Ahmed, R. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.4.1733 · Cited by 462 · see citing works
Discrete Generation of Superoxide and Hydrogen Peroxide by T Cell Receptor Stimulation
Devadas, S., Zaritskaya, L., Rhee, S. G., Oberley, L., & Williams, M. S. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20010659 · Cited by 458 · see citing works
T Cell Antigen Receptor-Mediated Activation of Phospholipase C Requires Tyrosine Phosphorylation
Mustelin, T., Coggeshall, K. M., Isakov, N., & Altman, A. (1990) · Science · doi:10.1126/science.2138816 · Cited by 456 · see citing works
Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice
Lee, T.-H. (2003) · Blood · doi:10.1182/blood-2002-08-2548 · Cited by 420 · see citing works
Yang, C. Y., Best, J. A., Knell, J., Yang, E., Sheridan, A. D., Jesionek, A. K., Li, H. S., Rivera, R. R., Lind, K. C., D’Cruz, L. M., et al. (2011) · Nature Immunology · doi:10.1038/ni.2158 · Cited by 411 · see citing works
Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II
Choi, M. H., Lee, I. K., Kim, G. W., Kim, B. U., Han, Y.-H., Yu, D.-Y., Park, H. S., Kim, K. Y., Lee, J. S., Choi, C., et al. (2005) · Nature · doi:10.1038/nature03587 · Cited by 403 · see citing works
Self-citationChae, H. Z., Kim, H. J., Kang, S. W., & Rhee, S. G. (1999) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(99)00037-6 · Cited by 390 · see citing works
Cutting Edge: Increased Expression of Bcl-2 in Antigen-Specific Memory CD8+ T Cells
Grayson, J. M., Zajac, A. J., Altman, J. D., & Ahmed, R. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.8.3950 · Cited by 349 · see citing works
Self-citationGeneration of effector CD8 + T cells and their conversion to memory T cells
Cui, W., & Kaech, S. M. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00926.x · Cited by 287 · see citing works
Low, F. M., Hampton, M. B., Peskin, A. V., & Winterbourn, C. C. (2006) · Blood · doi:10.1182/blood-2006-09-048728 · Cited by 281 · see citing works
Meng, T., Buckley, D. A., Galić, S., Tiganis, T., & Tonks, N. K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404606200 · Cited by 276 · see citing works
Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells
Ichii, H., Sakamoto, A., Hatano, M., Okada, S., Toyama, H., Taki, S., Arima, M., 嘉和, 黒., & Tokuhisa, T. (2002) · Nature Immunology · doi:10.1038/ni802 · Cited by 258 · see citing works
Insulin-stimulated intracellular hydrogen peroxide production in rat epididymal fat cells
May, J. M., & de Haën, C. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30209-0 · Cited by 235 · see citing works
Spatial Redox Regulation of a Critical Cysteine Residue of NF-κB in Vivo
Nishi, T., Shimizu, N., Hiramoto, M., Sato, I., Yamaguchi, Y., Hasegawa, M., Aizawa, S., Tanaka, H., Kataoka, K., Watanabe, H., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202970200 · Cited by 227 · see citing works
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 · see citing works
Self-citationRole for Bcl-6 in the generation and maintenance of memory CD8[+] T cells
市井, 啓. (2002) · Kobe University Repository Kernel (Kobe University) · Cited by 192 · see citing works
Piganelli, J. D., Flores, S. C., Cruz, C., Koepp, J., Batinic̈‐Haberle, I., Crapo, J. D., Day, B. J., Kachadourian, R., Young, R. L., Bradley, B., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.2.347 · Cited by 191 · see citing works
Secondary memory CD8+ T cells are more protective but slower to acquire a central–memory phenotype
Jabbari, A., & Harty, J. T. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052237 · Cited by 168 · see citing works
Structure of the sulphiredoxin–peroxiredoxin complex reveals an essential repair embrace
Jönsson, T. J., Johnson, L. C., & Lowther, W. T. (2008) · Nature · doi:10.1038/nature06415 · Cited by 144 · see citing works
Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation
Chaudhri, G., Clark, I. A., Hunt, N. H., Cowden, W. B., & Ceredig, R. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.137.8.2646 · Cited by 138 · cited 3× · see citing works
“These changes are critical because antioxidant treatment, which lowers ROI, decreases activation and proliferation (9).”
BackgroundYang, C., Lee, D., Song, C., An, S., Li, S., Kim, J., Kim, C., Yoo, D. G., Jeon, B. H., Yang, H., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061849 · Cited by 125 · see citing works
Self-citationReceptor‐stimulated oxidation of SHP‐2 promotes T‐cell adhesion through SLP‐76–ADAP
Kwon, J., Qu, C., Maeng, J.-S., Falahati, R., Lee, C., & Williams, M. S. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600706 · Cited by 124 · see citing works
The Requirement of Reversible Cysteine Sulfenic Acid Formation for T Cell Activation and Function
Michalek, R. D., Nelson, K. J., Holbrook, B. C., Yi, J. S., Stridiron, D., Daniel, L. W., Fetrow, J. S., King, S. B., Poole, L. B., & Grayson, J. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.6456 · Cited by 112 · see citing works
Self-citationCase, A. J., McGill, J. L., Tygrett, L. T., Shirasawa, T., Spitz, D. R., Waldschmidt, T. J., Legge, K. L., & Domann, F. E. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.11.025 · Cited by 107 · see citing works
Increased expression of peroxiredoxin II confers resistance to cisplatin.
Chung, Y. M., Yoo, Y. D., Park, J. K., Kim, Y. T., & Kim, H. J. (2001) · PubMed · Cited by 98 · see citing works
Imboden, J. B., & Weiss, A. (1987) · Biochemical Journal · doi:10.1042/bj2470695 · Cited by 89 · see citing works
MITOCHONDRIAL DYSFUNCTION IN T CELLS OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Perl, A., Gergely, P., & Banki, K. (2004) · International Reviews of Immunology · doi:10.1080/08830180490452576 · Cited by 82 · see citing works
Alexander‐Miller, M. A. (2004) · Immunologic Research · doi:10.1385/ir:31:1:13 · Cited by 72 · see citing works
Electron Transport Complex I Is Required for CD8+ T Cell Function
Yi, J. S., Holbrook, B. C., Michalek, R. D., Laniewski, N. G., & Grayson, J. M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.852 · Cited by 69 · see citing works
Self-citationLaniewski, N. G., & Grayson, J. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.20.11246-11257.2004 · Cited by 55 · see citing works
Self-citationCayota, A., Vuillier, F., Gonzalez, G. A., & Dighiero, G. (1996) · Blood · doi:10.1182/blood.v87.11.4746.bloodjournal87114746 · Cited by 49 · see citing works
T lymphocytes and dendritic cells are activated by the deletion of peroxiredoxin II (Prx II) gene
Moon, E., Noh, Y.-W., Han, Y., Kim, S.-U., Kim, J., Yu, D., & Lim, J. (2005) · Immunology Letters · doi:10.1016/j.imlet.2005.09.003 · Cited by 48 · see citing works
Self-citationShlomai, J. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.3029 · Cited by 47 · see citing works
Gopalakrishna, R., Gundimeda, U., Schiffman, J., & Mcneill, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801519200 · Cited by 43 · see citing works
Redox regulation of the proteasome in T lymphocytes during aging
Das, R., Ponnappan, S., & Ponnappan, U. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.11.020 · Cited by 36 · see citing works
Tebo, A. E., Fuller, M. J., Gaddis, D. E., Kojima, K., Rehani, K., & Zajac, A. J. (2005) · Journal of Virology · doi:10.1128/jvi.79.20.12703-12713.2005 · Cited by 27 · see citing works
Zenewicz, L. A., Foulds, K. E., Jiang, J. K., Fan, X., & Shen, H. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5805 · Cited by 26 · see citing works
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Avitabile, D., Ranieri, D., Nicolussi, A., D'inzeo, S., Capriotti, A. L., Genovese, L., Proietti, S., Cucina, A., Coppa, A., Samperi, R., et al. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.04.024 · Cited by 28 · see citing works
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- Authors
- Michalek, R. D., Crump, K. E., Weant, A. E., Hiltbold, E. M., Juneau, D. G., Moon, E.-Y., Yu, D.-Y., Poole, L. B., & Grayson, J. M.
- Affiliations
- Metabolon (United States) (US)
- Wake Forest University Health Sciences (US)
- Sejong University (KR)
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2012-12-15
- Volume
- 86
- Issue
- 24
- Pages
- 13629-13641
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC3503052
- OpenAlex
- W1993723357
- Cited by
- 17
- References
- 54
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 1 · 2022: 1 · 2020: 3 · 2017: 1 · 2016: 1 · 2014: 4 · 2013: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- KRIBB Repository (submittedVersion)
- Funders
- National Cancer Institute (CA126659, R33CA126659)
- National Institute of General Medical Sciences (GM050389, R01GM050389)
- National Institute of Allergy and Infectious Diseases (R01AI068952, T32AI007401)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- peroxiredoxin 2, CD8+ T cells, reactive oxygen species, hydrogen peroxide, T cell receptor stimulation, effector T cell expansion, chronic viral infection, immunopathology, antioxidant enzymes
- MeSH terms
- Animals, Immunologic Memory, Mice, Transgenic, Blotting, Western, CD8-Positive T-Lymphocytes, Cell Proliferation, Mice, Peroxiredoxins, Real-Time Polymerase Chain Reaction
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