Hogan, T., Shuvaev, A., Commenges, D., Yates, A. , Callard, R., Thiebaut, R. and Seddon, B. (2013) Clonally diverse T cell homeostasis is maintained by a common program of cell-cycle control. Journal of Immunology, 190(8), pp. 3985-3993. (doi: 10.4049/jimmunol.1203213)
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Publisher's URL: http://dx.doi.org/10.4049/jimmunol.1203213
Abstract
Lymphopenia induces T cells to undergo cell divisions as part of a homeostatic response mechanism. The clonal response to lymphopenia is extremely diverse, and it is unknown whether this heterogeneity represents distinct mechanisms of cell-cycle control or whether a common mechanism can account for the diversity. We addressed this question by combining in vivo and mathematical modeling of lymphopenia-induced proliferation (LIP) of two distinct T cell clonotypes. OT-I T cells undergo rapid LIP accompanied by differentiation that superficially resembles Ag-induced proliferation, whereas F5 T cells divide slowly and remain naive. Both F5 and OT-I LIP responses were most accurately described by a single stochastic division model where the rate of cell division was exponentially decreased with increasing cell numbers. The model successfully identified key biological parameters of the response and accurately predicted the homeostatic set point of each clone. Significantly, the model was successful in predicting interclonal competition between OT-I and F5 T cells, consistent with competition for the same resource(s) required for homeostatic proliferation. Our results show that diverse and heterogenous clonal T cell responses can be accounted for by a single common model of homeostasis.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Yates, Professor Andrew |
| Authors: | Hogan, T., Shuvaev, A., Commenges, D., Yates, A., Callard, R., Thiebaut, R., and Seddon, B. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Immunology |
| Journal Abbr.: | J. Immunol. |
| Publisher: | American Association of Immunologists |
| ISSN: | 0022-1767 |
| ISSN (Online): | 1550-6606 |
| Copyright Holders: | Copyright © 2013 The Authors |
| First Published: | First published in Journal of Immunology 190(8):3985-3993 |
| Publisher Policy: | Reproduced under a Creative Commons License |
| Related URLs: |
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