Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age

<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>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2015

Author dc:creator

• Bolner, Michelle L

Contributors dc:contributor

• Ellen Richie, PhD`
• Shawn Bratton, PhD
• David Johnson, PhD

• Recent thymic emigrant
• mature naive T cells
• Cyclin D1
• thymocyte development
• peripheral T cells
• Cell Biology
• Immunology and Infectious Disease
• Molecular Biology
• Molecular Genetics

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/636

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1671