Sinclair, C., Bains, I., Yates, A. J. and Seddon, B. (2013) Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive immune system. Proceedings of the National Academy of Sciences of the United States of America, 110(31), E2905-E2914. (doi: 10.1073/pnas.1304859110)
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Publisher's URL: http://dx.doi.org/10.1073/pnas.1304859110
Abstract
It has long been recognized that the T-cell compartment has more CD4 helper than CD8 cytotoxic T cells, and this is most evident looking at T-cell development in the thymus. However, it remains unknown how thymocyte development so favors CD4 lineage development. To identify the basis of this asymmetry, we analyzed development of synchronized cohorts of thymocytes in vivo and estimated rates of thymocyte death and differentiation throughout development, inferring lineage-specific efficiencies of selection. Our analysis suggested that roughly equal numbers of cells of each lineage enter selection and found that, overall, a remarkable ∼75% of cells that start selection fail to complete the process. Importantly it revealed that class I-restricted thymocytes are specifically susceptible to apoptosis at the earliest stage of selection. The importance of differential apoptosis was confirmed by placing thymocytes under apoptotic stress, resulting in preferential death of class I-restricted thymocytes. Thus, asymmetric death during selection is the key determinant of the CD4:CD8 ratio in which T cells are generated by thymopoiesis.
| Item Type: | Articles |
|---|---|
| Additional Information: | Andrew J. Yates and Benedict Seddon: joint corresponding authors. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Yates, Professor Andrew |
| Authors: | Sinclair, C., Bains, I., Yates, A. J., and Seddon, B. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Copyright Holders: | Copyright © 2013 The Authors |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 110(31):E2905-E2914 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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