CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation
CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation
The clonal expansion of antigen-specific CD8+ T cells in response to microbial infections is essential for adaptive immunity. Although IL-2 has been considered to be primarily responsible for this process, quantitatively normal expansion occurs in the absence of IL-2 receptor signaling. Here, we show that ligating CD27 on CD8+ T cells that have been stimulated through the T cell receptor causes their expansion in the absence of IL-2 by mediating two distinct cellular processes: enhancing cell cycling and promoting cell survival by maintaining the expression of IL-7 receptor alpha. This pathway for clonal expansion of the CD8+ T cell is not associated with the development of a capacity either for production of IFN-gamma or for cytotoxic T lymphocyte function and, therefore, is uncoupled from differentiation. Furthermore, ligating CD27 increases the threshold concentration at which IL-2 induces IFN-gamma-producing capability by the CD8+ T cell, suggesting that CD27 signaling may suppress effector differentiation. Finally, CD8+ T cells that have been stimulated by the TCR/CD27 pathway maintain their capacity for subsequent expansion and effector differentiation in response to a viral challenge in vivo. Thus, the TCR/CD27 pathway enables the CD8+ T cell to replicate by a process of self-renewal, which may contribute to the continuous generation of new effector CD8+ T cells in persistent viral infections.
19454-19459
Carr, James M.
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Carrasco, Marlene J.
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Thaventhiran, James E.D.
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Bambrough, Paul J.
a9c09bc2-2aa8-4f8b-905e-191b15803ab5
Kraman, Matthew
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Edwards, Alexander D.
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Al-Shamkhani, Aymen
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Fearon, Douglas T.
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2006
Carr, James M.
ea473769-43a4-4165-be86-2e760e45ab1f
Carrasco, Marlene J.
3504b18c-e3a4-43c9-b3c6-fc87cc434836
Thaventhiran, James E.D.
06fed5d0-2557-4f3e-97c1-84a520266525
Bambrough, Paul J.
a9c09bc2-2aa8-4f8b-905e-191b15803ab5
Kraman, Matthew
77979ffb-5f79-47b4-bc2f-11eef534c7d5
Edwards, Alexander D.
ac7dace7-1b41-4dac-903b-30c44f094b59
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Fearon, Douglas T.
8fae7801-5d8a-4a75-9dfe-e6052ebe01c8
Carr, James M., Carrasco, Marlene J., Thaventhiran, James E.D., Bambrough, Paul J., Kraman, Matthew, Edwards, Alexander D., Al-Shamkhani, Aymen and Fearon, Douglas T.
(2006)
CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation.
Proceedings of the National Academy of Sciences of the United States of America, 103 (51), .
(doi:10.1073/pnas.0609706104).
Abstract
The clonal expansion of antigen-specific CD8+ T cells in response to microbial infections is essential for adaptive immunity. Although IL-2 has been considered to be primarily responsible for this process, quantitatively normal expansion occurs in the absence of IL-2 receptor signaling. Here, we show that ligating CD27 on CD8+ T cells that have been stimulated through the T cell receptor causes their expansion in the absence of IL-2 by mediating two distinct cellular processes: enhancing cell cycling and promoting cell survival by maintaining the expression of IL-7 receptor alpha. This pathway for clonal expansion of the CD8+ T cell is not associated with the development of a capacity either for production of IFN-gamma or for cytotoxic T lymphocyte function and, therefore, is uncoupled from differentiation. Furthermore, ligating CD27 increases the threshold concentration at which IL-2 induces IFN-gamma-producing capability by the CD8+ T cell, suggesting that CD27 signaling may suppress effector differentiation. Finally, CD8+ T cells that have been stimulated by the TCR/CD27 pathway maintain their capacity for subsequent expansion and effector differentiation in response to a viral challenge in vivo. Thus, the TCR/CD27 pathway enables the CD8+ T cell to replicate by a process of self-renewal, which may contribute to the continuous generation of new effector CD8+ T cells in persistent viral infections.
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Published date: 2006
Organisations:
Cancer Sciences, Medicine
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Local EPrints ID: 44828
URI: http://eprints.soton.ac.uk/id/eprint/44828
ISSN: 0027-8424
PURE UUID: e3d9add2-d164-4fd4-a0fb-cd0a08eaebac
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Date deposited: 16 Mar 2007
Last modified: 16 Mar 2024 03:02
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Contributors
Author:
James M. Carr
Author:
Marlene J. Carrasco
Author:
James E.D. Thaventhiran
Author:
Paul J. Bambrough
Author:
Matthew Kraman
Author:
Alexander D. Edwards
Author:
Douglas T. Fearon
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