Type of Document Master's Thesis Author Pryputniewicz, Sarah Jean III Author's Email Address email@example.com 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
- differential regulation
- activated T cells
- lymph nodes
Date of Defense 1997-12-01 Availability unrestricted Abstract2, 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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