Title page for ETD etd-11397-10254


Type of Document Master's Thesis
Author Pryputniewicz, Sarah Jean III
Author's Email Address spryputn@gte.net
URN etd-11397-10254
Title Mechanism of TCDD-Induced Immunotoxicity: The Role of Cell Activation in the Generation of Toxicity
Degree Master of Science
Department Biology
Advisory Committee
Advisor Name Title
Bevan, David R.
Ehrich, Marion F.
Nagarkatti, Mitzi
Nagarkatti, Prakash S. Committee Chair
Keywords
  • TCDD
  • apoptosis
  • differential regulation
  • activated T cells
  • lymph nodes
Date of Defense 1997-12-01
Availability unrestricted
Abstract
2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin is well known for its immunotoxic effects on the thymus,

as well as on B and T lymphocyte functions. Previous studies suggested that TCDD exerted

immunotoxic effects only on cells differentiating in response to antigenic challenge. To this date,

no work has been done to characterize the long-term effects of TCDD on the activated cells.

Additionally, no studies have been done to determine whether TCDD has any effect on resting T

cells. In the current study, therefore, we investigated the effects of TCDD on activated and resting

cells within the same animal. T cells in the popliteal lymph node cells were activated by rear

footpad immunizations with anti-CD3 antibodies. Distally-located axillary lymph nodes were

chosen as a source of naive and resting T cells. Our results demonstrate that TCDD acted at the

time of cell differentiation to suppress the immune responses of activated T cells, but failed to

suppress, and at times, enhanced the immune responses of resting T cells. The TCDD-induced

immunomodulations were temporary; responsiveness of both activated and resting T cells from

TCDD-treated animals returned to normal by two weeks post-treatment, suggesting that TCDD

does not affect memory cells. Futhermore, we provide direct evidence that the TCDD-induced

immunosuppression in activated cells is due to increased apoptosis of CD3+ T cells. TCDD also

induced significant changes in cell surface markers expressed by naive and activated T cells.

Together our data suggested that TCDD suppresses the proliferative responsiveness of only the

activated, but not naive, T cells and that this is accomplished by induction of increased apoptosis of

activated T cells. These studies shed new light on the mechanism through which TCDD induces

increased susceptibility to infections and cancer in the vertebrate host.

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 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  Abbreviations.pdf 3.27 Kb < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01
  Abstract.pdf 3.70 Kb 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01
  Acknowledgments.pdf 4.37 Kb 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01
  Appendix_A.pdf 14.85 Kb 00:00:04 00:00:02 00:00:01 < 00:00:01 < 00:00:01
  Appendix_B.pdf 5.33 Kb 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01
  BodyofThesis.pdf 275.74 Kb 00:01:16 00:00:39 00:00:34 00:00:17 00:00:01
  Dedication.pdf 3.66 Kb 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01
  Figures16-19.pdf 278.21 Kb 00:01:17 00:00:39 00:00:34 00:00:17 00:00:01
  Figures2-15.pdf 106.36 Kb 00:00:29 00:00:15 00:00:13 00:00:06 < 00:00:01
  Figures20-21.pdf 133.30 Kb 00:00:37 00:00:19 00:00:16 00:00:08 < 00:00:01
  mouse.pdf 11.72 Kb 00:00:03 00:00:01 00:00:01 < 00:00:01 < 00:00:01
  Title.pdf 3.05 Kb < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01
  TOC.pdf 61.00 Kb 00:00:16 00:00:08 00:00:07 00:00:03 < 00:00:01

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