The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on T cell activation Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/m900nx92t

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • The immune system has been identified as a very sensitive target for the toxic effects of 2,3,7,S-tetrachlorodibenzo-p-dioxin (TCDD). Exposure to TCDD has been shown to disrupt the generation of both cell-mediated and humoral T cell-dependent immunity in laboratory animals; however, the mechanism remains unknown. In this dissertation, the hypothesis is tested that TCDD exposure alters T cell activation and differentiation either directly or by inhibiting the activation of antigen presenting cells (APC). Previous studies from our laboratory using the PSI5 tumor allograft model suggest that TCDD inhibited T cell activation by suppressing the induction of the costimulatory molecule CDS6 on B220+ and Mac-1+ cells. To address the effects of TCDD on APC, we further characterized the activation of splenic APC in the PSI5 model and found that TCDD suppressed the induction of the accessory molecules CDS6, CD54 and MHC II on APC as well as their production of IL-12. Although it was determined that the induction of these costimulatory molecules following PSI5 immunization was CD40independent, their in vivo expression could be enhanced by administering an agonistic antibody to CD40 to mice. APC from anti-CD40 treated mice expressed significantly higher levels of these accessory molecules and IL-12, and this enhanced APC activation was largely unaffected by TCDD. However, TCDD-treated mice receiving both P815 and anti-CD40 were unable to generate T cell-dependent allograft immunity suggesting that suppression of APC activation may not be underlying TCDD immunosuppression. To address the direct effects of TCDD on T cell activation, we adoptively-transferred DO11.10 TCR transgenic T cells into syngeneic recipients and monitored their activation in vivo following exposure to antigen. Although treatment of adoptively-transferred mice had no effect on the expansion or activation of the OVA-specific CD4+ T cells, the production of the T cell-derived cytokines IL-2, IFN-γ, IL-4 and IL-10 was suppressed. These data suggest that TCDD may suppress the differentiation of OVA-specific T cells into effector T helper cells which are capable of driving T cell-dependent immune responses.
Resource Type
Date Available
Date Copyright
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Committee Member
Academic Affiliation
Non-Academic Affiliation
Subject
Rights Statement
Peer Reviewed
Language
Digitization Specifications
  • File scanned at 300 ppi (Monochrome, 8-bit Grayscale, 24-bit Color) using ScandAll PRO 1.8.1 on a Fi-6670 in PDF format. CVista PdfCompressor 4.0 was used for pdf compression and textual OCR.
Replaces
Additional Information
  • description.provenance : Made available in DSpace on 2012-09-05T19:46:24Z (GMT). No. of bitstreams: 1 ShepherdDavidM2000.pdf: 5445384 bytes, checksum: e0687927636ec68e493f9e7fa162210a (MD5) Previous issue date: 1999-07-28
  • description.provenance : Submitted by Kaylee Patterson (kdpscanner@gmail.com) on 2012-08-29T17:05:22Z No. of bitstreams: 1 ShepherdDavidM2000.pdf: 5445384 bytes, checksum: e0687927636ec68e493f9e7fa162210a (MD5)
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2012-08-30T18:33:49Z (GMT) No. of bitstreams: 1 ShepherdDavidM2000.pdf: 5445384 bytes, checksum: e0687927636ec68e493f9e7fa162210a (MD5)
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2012-09-05T19:46:24Z (GMT) No. of bitstreams: 1 ShepherdDavidM2000.pdf: 5445384 bytes, checksum: e0687927636ec68e493f9e7fa162210a (MD5)

Relationships

Parents:

This work has no parents.

Last modified

Downloadable Content

Download PDF

Items