The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Malmberg, K.-J.
Right arrow Articles by Kiessling, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malmberg, K.-J.
Right arrow Articles by Kiessling, R.
The Journal of Immunology, 2001, 167: 2595-2601.
Copyright © 2001 by The American Association of Immunologists

Inhibition of Activated/Memory (CD45RO+) T Cells by Oxidative Stress Associated with Block of NF-{kappa}B Activation1

Karl-Johan Malmberg2,*, Velmurugesan Arulampalam{dagger}, Fumiko Ichihara*, Max Petersson*,{ddagger}, Kazutake Seki*, Tove Andersson{dagger}, Rodica Lenkei§, Giuseppe Masucci*, Sven Pettersson{ddagger} and Rolf Kiessling*,{ddagger}

* Immune and Gene Therapy Laboratory, Department of Oncology and Pathology, Cancer Center Karolinska, {dagger} Center for Genomic Research, and {ddagger} Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden; and § CALAB Research/NOVA Medical Flow Cytometry Laboratory, Stockholm, Sweden

Impaired immune responses in cancer patients have been associated with oxidative stress. Increased levels of reactive oxygen species released from activated, tumor-infiltrating macrophages or granulocytes may therefore constitute a hurdle for effective immunotherapy against cancer. In this study, we investigated functional consequences and molecular events in T cells exposed to low levels of oxidative stress. We observed that cytokine production of human PBMC, upon stimulation with an HLA-A*0201-restricted influenza peptide and nonspecific receptor cross-linking, was reduced after exposure to micromolar levels of H2O2. Functional impairment as measured by IFN-{gamma} release occurred earlier and at lower doses of exogenously added H2O2 than required to induce apoptosis. This suggests that there is a dose window of oxidative stress leading to T cell unresponsiveness in the absence of apoptosis. The reduction of Th1 cytokines, induced by H2O2, was predominantly observed in memory/effector (CD45RO+) T cells and correlated with a block in NF-{kappa}B activation. IL-10 production was more profoundly influenced by low doses of H2O2 than IFN-{gamma}, TNF-{alpha}, and IL-2. The influence of H2O2 on production of IL-10 was not significantly different between memory/activated and naive T cells. These observations suggest that Th1 and Th2 cytokines are differently regulated under conditions of oxidative stress. Taken together, these findings may explain why Ag-experienced, CD45RO+, T cells found in the tumor milieu are functionally suppressed.




This article has been cited by other articles:


Home page
 BloodHome page
D. Mougiakakos, C. C. Johansson, and R. Kiessling
Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death
Blood, April 9, 2009; 113(15): 3542 - 3545.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Ando, K. Mimura, C. C. Johansson, M. G. Hanson, D. Mougiakakos, C. Larsson, T. Martins da Palma, D. Sakurai, H. Norell, M. Li, et al.
Transduction with the Antioxidant Enzyme Catalase Protects Human T Cells against Oxidative Stress
J. Immunol., December 15, 2008; 181(12): 8382 - 8390.
[Abstract] [Full Text] [PDF]

Home page
 Ther Adv Respir DisHome page
A. Nadeem, A. Masood, and N. Siddiqui
Review: Oxidant--antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options
Therapeutic Advances in Respiratory Disease, August 1, 2008; 2(4): 215 - 235.
[Abstract] [PDF]

Home page
 J. Immunol.Home page
F. B. Thoren, A. I. Romero, S. Hermodsson, and K. Hellstrand
The CD16-/CD56bright Subset of NK Cells Is Resistant to Oxidant-Induced Cell Death
J. Immunol., July 15, 2007; 179(2): 781 - 785.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M.-L. Boulland, J. Marquet, V. Molinier-Frenkel, P. Moller, C. Guiter, F. Lasoudris, C. Copie-Bergman, M. Baia, P. Gaulard, K. Leroy, et al.
Human IL4I1 is a secreted L-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation
Blood, July 1, 2007; 110(1): 220 - 227.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Bhattacharyya, D. Mandal, G. S. Sen, S. Pal, S. Banerjee, L. Lahiry, J. H. Finke, C. S. Tannenbaum, T. Das, and G. Sa
Tumor-Induced Oxidative Stress Perturbs Nuclear Factor-{kappa}B Activity-Augmenting Tumor Necrosis Factor-{alpha}-Mediated T-Cell Death: Protection by Curcumin
Cancer Res., January 1, 2007; 67(1): 362 - 370.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Takahashi, M. G. V. Hanson, H. R. Norell, A. M. Havelka, K. Kono, K.-J. Malmberg, and R. V. R. Kiessling
Preferential Cell Death of CD8+ Effector Memory (CCR7-CD45RA-) T Cells by Hydrogen Peroxide-Induced Oxidative Stress
J. Immunol., May 15, 2005; 174(10): 6080 - 6087.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Ichihara, K. Kono, A. Takahashi, H. Kawaida, H. Sugai, and H. Fujii
Increased Populations of Regulatory T Cells in Peripheral Blood and Tumor-Infiltrating Lymphocytes in Patients with Gastric and Esophageal Cancers
Clin. Cancer Res., October 1, 2003; 9(12): 4404 - 4408.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Wang, R. A. Barke, R. Charboneau, H. H. Loh, and S. Roy
Morphine Negatively Regulates Interferon-{gamma} Promoter Activity in Activated Murine T Cells through Two Distinct Cyclic AMP-dependent Pathways
J. Biol. Chem., September 26, 2003; 278(39): 37622 - 37631.
[Abstract] [Full Text] [PDF]

Home page
 International Journal of ToxicologyHome page
H. Z. Rofael, R. M. Turkall, and M. S. Abdel-Rahman
Effect of Ketamine on Cocaine-Induced Immunotoxicity in Rats
International Journal of Toxicology, September 1, 2003; 22(5): 343 - 358.
[Abstract] [PDF]

Home page
 Clin. Cancer Res.Home page
K.-J. Malmberg, R. Lenkei, M. Petersson, T. Ohlum, F. Ichihara, B. Glimelius, J.-E. Frodin, G. Masucci, and R. Kiessling
A Short-Term Dietary Supplementation of High Doses of Vitamin E Increases T Helper 1 Cytokine Production in Patients with Advanced Colorectal Cancer
Clin. Cancer Res., June 1, 2002; 8(6): 1772 - 1778.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.