{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-2320"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-2320","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"The mechanism of T cell dysfunction induced by Diethylstilbestrol","abstract":"Estrogens have the ability to alter the immune system. Diethylstilbestrol (DES), asynthetic estrogen, is known to have estrogenic activity and induce thymic alterations.We investigated the mechanism by which DES is able to alter T cells and thus theimmune system. First, we studied the effect of DES on mature T cells by using the T cellleukemia cell line, Jurkat. We found that DES treatment reduced cell viability andincreased apoptosis. Additionally, apoptosis was found to involve both death receptorand mitochondria1 pathways. Furthermore, estrogen receptor beta was found to beexpressed in these cells and increased following DES treatment. Secondly, we studiedthe effect of DES on developing T cells using two different mouse models, timed pregnant and HY-TCR transgenic. The pregnant mouse model showed that DESexposure in utero reduced thymic cell viability and induced apoptosis at gestational day(gd)-17. Apoptosis was found to involve the death receptor pathway. Additionally,alterations in T cell subsets was most pronounced at gd-17 as well. The HY-TCR tgmouse model showed that DES exposure altered both positive and negative selection of Tcells. Furthermore, DES was found to alter the ability of T cells to proliferate during animmune response. Finally, we studied the intrathymic interaction between thymicstromal cells and thymic T cells. We found that cel1:cell interaction was important forinducing T cell apoptosis in the thymus. Additionally, FasL expression was increased onthymic stromal cells following DES exposure. Furthermore, the presence of both FasL onstromal cells and Fas on T cells was important for inducing T cell apoptosis in thethymus.","abstract_html":"Estrogens have the ability to alter the immune system. Diethylstilbestrol (DES), asynthetic estrogen, is known to have estrogenic activity and induce thymic alterations.We investigated the mechanism by which DES is able to alter T cells and thus theimmune system. First, we studied the effect of DES on mature T cells by using the T cellleukemia cell line, Jurkat. We found that DES treatment reduced cell viability andincreased apoptosis. Additionally, apoptosis was found to involve both death receptorand mitochondria1 pathways. Furthermore, estrogen receptor beta was found to beexpressed in these cells and increased following DES treatment. Secondly, we studiedthe effect of DES on developing T cells using two different mouse models, timed pregnant and HY-TCR transgenic. The pregnant mouse model showed that DESexposure in utero reduced thymic cell viability and induced apoptosis at gestational day(gd)-17. Apoptosis was found to involve the death receptor pathway. Additionally,alterations in T cell subsets was most pronounced at gd-17 as well. The HY-TCR tgmouse model showed that DES exposure altered both positive and negative selection of Tcells. Furthermore, DES was found to alter the ability of T cells to proliferate during animmune response. Finally, we studied the intrathymic interaction between thymicstromal cells and thymic T cells. We found that cel1:cell interaction was important forinducing T cell apoptosis in the thymus. Additionally, FasL expression was increased onthymic stromal cells following DES exposure. Furthermore, the presence of both FasL onstromal cells and Fas on T cells was important for inducing T cell apoptosis in thethymus.","abstract_has_math":false,"creators":["Brown, Nicole Chantae"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":"Microbiology & Immunology","degree_department":null,"school":null,"contributors":["Dr. Mitzi Nagarkatti"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2005,"date_issued":"2005-01-01T08:00:00Z","date_published":"2005-01-01T08:00:00Z","updated_at":"2026-07-24T05:55:14Z","subjects":["estrogen","synthetic estrogen","immune system","Jurkat","apoptosis","gestational day","gd-17","HY-TCR tg","Medicine and Health Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/1321"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/1321","href":"https://scholarscompass.vcu.edu/etd/1321","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/18MQ-P731","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr. Mitzi Nagarkatti"]},{"key":"dc:creator","label":"Author","values":["Brown, Nicole Chantae"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-07-09T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology & Immunology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["estrogen","synthetic estrogen","immune system","Jurkat","apoptosis","gestational day","gd-17","HY-TCR tg","Medicine and Health Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/18MQ-P731","https://scholarscompass.vcu.edu/etd/1321"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Estrogens have the ability to alter the immune system. Diethylstilbestrol (DES), asynthetic estrogen, is known to have estrogenic activity and induce thymic alterations.We investigated the mechanism by which DES is able to alter T cells and thus theimmune system. First, we studied the effect of DES on mature T cells by using the T cellleukemia cell line, Jurkat. We found that DES treatment reduced cell viability andincreased apoptosis. Additionally, apoptosis was found to involve both death receptorand mitochondria1 pathways. Furthermore, estrogen receptor beta was found to beexpressed in these cells and increased following DES treatment. Secondly, we studiedthe effect of DES on developing T cells using two different mouse models, timed pregnant and HY-TCR transgenic. The pregnant mouse model showed that DESexposure in utero reduced thymic cell viability and induced apoptosis at gestational day(gd)-17. Apoptosis was found to involve the death receptor pathway. Additionally,alterations in T cell subsets was most pronounced at gd-17 as well. The HY-TCR tgmouse model showed that DES exposure altered both positive and negative selection of Tcells. Furthermore, DES was found to alter the ability of T cells to proliferate during animmune response. Finally, we studied the intrathymic interaction between thymicstromal cells and thymic T cells. We found that cel1:cell interaction was important forinducing T cell apoptosis in the thymus. Additionally, FasL expression was increased onthymic stromal cells following DES exposure. Furthermore, the presence of both FasL onstromal cells and Fas on T cells was important for inducing T cell apoptosis in thethymus."]},{"key":"dc:title","label":"Title","values":["The mechanism of T cell dysfunction induced by Diethylstilbestrol"]}]}],"canonical_facts":{"dc:contributor":["Dr. Mitzi Nagarkatti"],"dc:creator":["Brown, Nicole Chantae"],"dc:date.available":["2014-07-09T07:00:00Z"],"dc:description.abstract":["Estrogens have the ability to alter the immune system. Diethylstilbestrol (DES), asynthetic estrogen, is known to have estrogenic activity and induce thymic alterations.We investigated the mechanism by which DES is able to alter T cells and thus theimmune system. First, we studied the effect of DES on mature T cells by using the T cellleukemia cell line, Jurkat. We found that DES treatment reduced cell viability andincreased apoptosis. Additionally, apoptosis was found to involve both death receptorand mitochondria1 pathways. Furthermore, estrogen receptor beta was found to beexpressed in these cells and increased following DES treatment. Secondly, we studiedthe effect of DES on developing T cells using two different mouse models, timed pregnant and HY-TCR transgenic. The pregnant mouse model showed that DESexposure in utero reduced thymic cell viability and induced apoptosis at gestational day(gd)-17. Apoptosis was found to involve the death receptor pathway. Additionally,alterations in T cell subsets was most pronounced at gd-17 as well. The HY-TCR tgmouse model showed that DES exposure altered both positive and negative selection of Tcells. Furthermore, DES was found to alter the ability of T cells to proliferate during animmune response. Finally, we studied the intrathymic interaction between thymicstromal cells and thymic T cells. We found that cel1:cell interaction was important forinducing T cell apoptosis in the thymus. Additionally, FasL expression was increased onthymic stromal cells following DES exposure. Furthermore, the presence of both FasL onstromal cells and Fas on T cells was important for inducing T cell apoptosis in thethymus."],"dc:identifier":["https://doi.org/10.25772/18MQ-P731","https://scholarscompass.vcu.edu/etd/1321"],"dc:rights":["© The Author"],"dc:subject":["estrogen","synthetic estrogen","immune system","Jurkat","apoptosis","gestational day","gd-17","HY-TCR tg","Medicine and Health Sciences"],"dc:title":["The mechanism of T cell dysfunction induced by Diethylstilbestrol"],"thesis:degree_discipline":["Microbiology & Immunology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:55:14Z"}