The University of Southampton
University of Southampton Institutional Repository

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
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.
0027-8424
19454-19459
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.
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), 19454-19459. (doi:10.1073/pnas.0609706104).

Record type: Article

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.

This record has no associated files available for download.

More information

Published date: 2006
Organisations: Cancer Sciences, Medicine

Identifiers

Local EPrints ID: 44828
URI: http://eprints.soton.ac.uk/id/eprint/44828
ISSN: 0027-8424
PURE UUID: e3d9add2-d164-4fd4-a0fb-cd0a08eaebac
ORCID for Aymen Al-Shamkhani: ORCID iD orcid.org/0000-0003-0727-4189

Catalogue record

Date deposited: 16 Mar 2007
Last modified: 16 Mar 2024 03:02

Export record

Altmetrics

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×