Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

2,3,7,8-Tetrachlorodibenzo-p-dioxin Enhances Negative Selection of T Cells in the Thymus but Allows Autoreactive T Cells to Escape Deletion and Migrate to the Periphery

Michael T. Fisher, Mitzi Nagarkatti and Prakash S. Nagarkatti
Molecular Pharmacology January 2005, 67 (1) 327-335; DOI: https://doi.org/10.1124/mol.104.005868
Michael T. Fisher
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitzi Nagarkatti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Prakash S. Nagarkatti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental pollutant, has been shown to cause thymic atrophy and apoptosis. However, whether TCDD alters the process of T-cell selection in the thymus is not clear. To this end, we investigated the effects of TCDD in the context of the HY-T-cell receptor (TCR) transgenic (Tg) mouse model. We noted that negatively selecting male HY-TCR Tg mice were significantly more sensitive to the thymotoxic effects of TCDD relative to positively selecting female HY-TCR Tg mice, including increased reduction in cellularity and increased induction of apoptosis. TCDD exposure also altered the thymocyte subset composition in HY-TCR Tg male but not female mice. In addition, TCDD treatment resulted in increased extracellularly regulated kinase phosphorylation and lymphocyte-specific protein tyrosine kinase expression in thymocytes of HY-TCR Tg male but not female mice. The increase in proportion of CD8+ mature thymocytes noted in HY-TCR Tg male mice was reflected in the periphery, with TCDD-exposed HY-TCR Tg male mice having increased numbers of CD8+ T cells. Finally, we noted that the proliferative response of HY-TCR Tg male T cells to HY(self)-Ag was enhanced after exposure to TCDD, whereas that of HY-TCR Tg female mice was decreased. Taken together, these data suggest that TCDD alters the process of thymic selection, possibly by enhancing negative thymocyte selection, whereas at the same time allowing autoreactive T cells to escape deletion in the thymus and immigrate to the periphery.

  • Received August 6, 2004.
  • Accepted October 15, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 67 (1)
Molecular Pharmacology
Vol. 67, Issue 1
1 Jan 2005
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
2,3,7,8-Tetrachlorodibenzo-p-dioxin Enhances Negative Selection of T Cells in the Thymus but Allows Autoreactive T Cells to Escape Deletion and Migrate to the Periphery
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

2,3,7,8-Tetrachlorodibenzo-p-dioxin Enhances Negative Selection of T Cells in the Thymus but Allows Autoreactive T Cells to Escape Deletion and Migrate to the Periphery

Michael T. Fisher, Mitzi Nagarkatti and Prakash S. Nagarkatti
Molecular Pharmacology January 1, 2005, 67 (1) 327-335; DOI: https://doi.org/10.1124/mol.104.005868

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

2,3,7,8-Tetrachlorodibenzo-p-dioxin Enhances Negative Selection of T Cells in the Thymus but Allows Autoreactive T Cells to Escape Deletion and Migrate to the Periphery

Michael T. Fisher, Mitzi Nagarkatti and Prakash S. Nagarkatti
Molecular Pharmacology January 1, 2005, 67 (1) 327-335; DOI: https://doi.org/10.1124/mol.104.005868
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • GABAAR Molecular Identity in Oligodendrocytes
  • Editing TOP2α Intron-19 5′ SS Circumvents Drug Resistance
  • SerpinA3N and drug induced liver injury
Show more Article

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics