The absence of thymus involution in K5.Cyclin D1 transgenic mice sustains the output of recent thymic emigrants during aging. (LYM7P.717)
| Autor: | Michelle Bolner, Pamela Fink, Ellen Richie |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:193.5-193.5 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.192.supp.193.5 |
| Popis: | Naïve T cells are continually exported from the thymus and maintain peripheral TCR repertoire diversity. As the thymus involutes with age, thymopoiesis and T cell output wane, reducing the number of recent thymic emigrants (RTEs). Although homeostatic proliferation of memory T cells sustains peripheral T cell numbers, the decrease in naïve T cells restricts immune responsiveness to new antigens. It has been proposed that RTE output would be sustained if thymus involution were prevented. To test this hypothesis, we analyzed RTEs in mice that do not undergo thymus involution due to a keratin 5 promoter-driven Cyclin D1 transgene (K5.D1) expressed in thymic epithelial cells. This transgene maintains functional thymic microenvironmental niches that support thymocyte progenitor maturation. We introduced a RAG2p-GFP transgene to discriminate RTEs from mature naïve (MN) T cells in K5.D1 mice. As previously reported, RTEs decline with age in RAG2p-GFP controls. In contrast, the number of RTEs increases with age in K5.D1;RAG2p-GFP mice. Despite a lower frequency of MN T cells in K5.D1 mice, the number of MN T cells is increased by ~4 fold in 5-6 month old K5.D1;RAG2p-GFP mice compared to RAG2p-GFP littermates. The increase in naïve T cells does not displace existing memory T cells, supporting the notion that naïve and memory T cells occupy distinct homeostatic niches. These data demonstrate that preventing thymus involution sustains the naïve T cell compartment during aging. |
| Databáze: | OpenAIRE |
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