Skip Navigation



ToxSci Advance Access published online on May 2, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg110
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
74/1/74    most recent
kfg110v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Mitchell, K. A.
Right arrow Articles by Lawrence, B. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mitchell, K. A.
Right arrow Articles by Lawrence, B. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received February 20, 2003; accepted April 3, 2003
© 2003 Society of Toxicology

Immunotoxicology

Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Renders Influenza Virus-Specific CD8+ T Cells Hyporesponsive to Antigen

Kristen A. Mitchell 1 B. Paige Lawrence 1*

1 Graduate Program in Pharmacology/Toxicology, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164

* To whom correspondence should be addressed. E-mail: bpl{at}mail.wsu.edu.


  Abstract

While considerable evidence indicates that exposure to the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs T cell function, the precise mechanism underlying this effect is not well understood. Furthermore, relatively little is known about the effects of TCDD on the fate of activated, antigen-specific T cells in vivo. In the present study, we took advantage of MHC class I-restricted tetramers and clonotypic anti-TCR antibodies to follow the fate of influenza virus-specific CD8+ T cells in mice treated with TCDD. Exposure to TCDD suppressed the clonal expansion of influenza virus-specific CD8+ T cells, resulting in a three- to five-fold reduction in the number of cytotoxic T lymphocytes (CTL) in the lymph node, as compared to vehicle-treated mice. Studies to address possible mechanisms for the diminished CTL response failed to show evidence for increased apoptosis in virus-specific CD8+ T cells from TCDD-exposed mice. However, treatment with TCDD reduced the number of proliferating virus-specific CD8+ T cells by as much as 70% on day 7 post infection. Moreover, ex vivo restimulation of lymph node cells with influenza virus nucleoprotein (NP366-374) peptide and exogenous IL-2 only partially restored the proliferation in influenza virus-specific CD8+ T cells from TCDD-exposed mice, and failed to stimulate IFN{gamma} production by these cells. The observation that neither proliferation nor IFN{gamma} production by CD8+ T cells could be completely restored, even when cells were provided with optimal stimulation, suggests that exposure to TCDD drives antigen-specific CD8+ T cells into a state of unresponsiveness similar to anergy.

Key Words: TCDD (dioxin), immunosuppression, CD8+ T lymphocytes, antigen-specific, tetramer, influenza virus, anergy, mouse, lymph node, in vivo .


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
N. B. Marshall, W. R. Vorachek, L. B. Steppan, D. V. Mourich, and N. I. Kerkvliet
Functional Characterization and Gene Expression Analysis of CD4+CD25+ Regulatory T Cells Generated in Mice Treated with 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
J. Immunol., August 15, 2008; 181(4): 2382 - 2391.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. Teske, A. A. Bohn, J. P. Hogaboam, and B. P. Lawrence
Aryl Hydrocarbon Receptor Targets Pathways Extrinsic to Bone Marrow Cells to Enhance Neutrophil Recruitment during Influenza Virus Infection
Toxicol. Sci., March 1, 2008; 102(1): 89 - 99.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Neff-LaFord, S. Teske, T. P. Bushnell, and B. P. Lawrence
Aryl Hydrocarbon Receptor Activation during Influenza Virus Infection Unveils a Novel Pathway of IFN-{gamma} Production by Phagocytic Cells
J. Immunol., July 1, 2007; 179(1): 247 - 255.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. P. Lawrence, A. D. Roberts, J. J. Neumiller, J. A. Cundiff, and D. L. Woodland
Aryl Hydrocarbon Receptor Activation Impairs the Priming but Not the Recall of Influenza Virus-Specific CD8+ T Cells in the Lung
J. Immunol., November 1, 2006; 177(9): 5819 - 5828.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C. J. Funatake, E. A. Dearstyne, L. B. Steppan, D. M. Shepherd, E. S. Spanjaard, A. Marshak-Rothstein, and N. I. Kerkvliet
Early Consequences of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure on the Activation and Survival of Antigen-Specific T Cells
Toxicol. Sci., November 1, 2004; 82(1): 129 - 142.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
B. P. Lawrence and B. A. Vorderstrasse
Activation of the Aryl Hydrocarbon Receptor Diminishes the Memory Response to Homotypic Influenza Virus Infection but Does Not Impair Host Resistance
Toxicol. Sci., June 1, 2004; 79(2): 304 - 314.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
D. H. Sherr
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Long Term Immunologic Memory
Toxicol. Sci., June 1, 2004; 79(2): 211 - 213.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.