The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the age-associated decline of naïve T cells in the periphery. We find that K5.D1 recent thymic emigrants (RTEs) undergo typical phenotypic maturation. In addition, functional studies show that K5.D1 peripheral T cells are responsive to anti-CD3 and anti-CD28 stimulation in vitro. Competitive adoptive transfer studies with K5.D1 and nontransgenic RTEs indicate that K5.D1 RTEs are incorporated into the peripheral T cell pool comparably to nontransgenic controls. However, K5.D1 mature naïve (MN) T cells out-persist control counterparts, which likely occurs, in part, to increased expression of the cytokine receptor IL-7Rα. Collectively, these data show that preventing thymus involution not only sustains T cell output to maintain naïve T cell numbers, but also provides functionally competent MN T cells during aging.
","abstract_html":"<p>The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the age-associated decline of naïve T cells in the periphery. We find that K5.D1 recent thymic emigrants (RTEs) undergo typical phenotypic maturation. In addition, functional studies show that K5.D1 peripheral T cells are responsive to anti-CD3 and anti-CD28 stimulation <em>in vitro</em>. Competitive adoptive transfer studies with K5.D1 and nontransgenic RTEs indicate that K5.D1 RTEs are incorporated into the peripheral T cell pool comparably to nontransgenic controls. However, K5.D1 mature naïve (MN) T cells out-persist control counterparts, which likely occurs, in part, to increased expression of the cytokine receptor IL-7Rα. Collectively, these data show that preventing thymus involution not only sustains T cell output to maintain naïve T cell numbers, but also provides functionally competent MN T cells during aging.</p>","abstract_has_math":false,"creators":["Bolner, Michelle L"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Ellen Richie, PhD`","Shawn Bratton, PhD","David Johnson, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-12-01T08:00:00Z","date_published":"2015-12-01T08:00:00Z","updated_at":"2026-07-24T05:48:59Z","subjects":["Recent thymic emigrant","mature naive T cells","Cyclin D1","thymocyte development","peripheral T cells","Cell Biology","Immunology and Infectious Disease","Molecular Biology","Molecular Genetics"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/636","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Ellen Richie, PhD`","Shawn Bratton, PhD","David Johnson, PhD"]},{"key":"dc:creator","label":"Author","values":["Bolner, Michelle L"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-12-03T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Recent thymic emigrant","mature naive T cells","Cyclin D1","thymocyte development","peripheral T cells","Cell Biology","Immunology and Infectious Disease","Molecular Biology","Molecular Genetics"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/636"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the age-associated decline of naïve T cells in the periphery. We find that K5.D1 recent thymic emigrants (RTEs) undergo typical phenotypic maturation. In addition, functional studies show that K5.D1 peripheral T cells are responsive to anti-CD3 and anti-CD28 stimulation in vitro. Competitive adoptive transfer studies with K5.D1 and nontransgenic RTEs indicate that K5.D1 RTEs are incorporated into the peripheral T cell pool comparably to nontransgenic controls. However, K5.D1 mature naïve (MN) T cells out-persist control counterparts, which likely occurs, in part, to increased expression of the cytokine receptor IL-7Rα. Collectively, these data show that preventing thymus involution not only sustains T cell output to maintain naïve T cell numbers, but also provides functionally competent MN T cells during aging.
"]},{"key":"dc:title","label":"Title","values":["Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age"]}]}],"canonical_facts":{"dc:contributor":["Ellen Richie, PhD`","Shawn Bratton, PhD","David Johnson, PhD"],"dc:creator":["Bolner, Michelle L"],"dc:date.available":["2016-12-03T08:00:00Z"],"dc:description.abstract":["The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the age-associated decline of naïve T cells in the periphery. We find that K5.D1 recent thymic emigrants (RTEs) undergo typical phenotypic maturation. In addition, functional studies show that K5.D1 peripheral T cells are responsive to anti-CD3 and anti-CD28 stimulation in vitro. Competitive adoptive transfer studies with K5.D1 and nontransgenic RTEs indicate that K5.D1 RTEs are incorporated into the peripheral T cell pool comparably to nontransgenic controls. However, K5.D1 mature naïve (MN) T cells out-persist control counterparts, which likely occurs, in part, to increased expression of the cytokine receptor IL-7Rα. Collectively, these data show that preventing thymus involution not only sustains T cell output to maintain naïve T cell numbers, but also provides functionally competent MN T cells during aging.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/636"],"dc:subject":["Recent thymic emigrant","mature naive T cells","Cyclin D1","thymocyte development","peripheral T cells","Cell Biology","Immunology and Infectious Disease","Molecular Biology","Molecular Genetics"],"dc:title":["Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:48:59Z"}