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International Immunology Advance Access originally published online on November 14, 2008
International Immunology 2009 21(1):29-42; doi:10.1093/intimm/dxn120
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© The Author 2008. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press and The Japanese Society for Immunology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

IL-2 receptor {gamma} chain cytokines differentially regulate human CD8+CD127+ and CD8+CD127– T cell division and susceptibility to apoptosis

Angela M. Crawley1,2, Tanya Katz1,2, Karl Parato2 and Jonathan B. Angel1,2,4

1 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada
2 Ottawa Health Research Institute, Ottawa, Ontario, Canada
3 Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
4 Division of Infectious Diseases, Ottawa Hospital—General Campus, 501 Smyth Road, Room G-12, Ottawa, Ontario K1H 8L6, Canada

Correspondence to: J. B. Angel; E-mail: jangel{at}ohri.ca

Expression of IL-7 receptor {alpha} (CD127) is associated with naive and memory (i.e. non-effector) CD8+ T cell phenotypes. Effector CD8+ T cells are predominantly CD127– and most die by apoptosis. Therefore, CD127 appears to be a marker for CD8+ T cell differentiation, yet its role in CD8+ T cell survival and memory development is unclear. To address this, we investigated the cell death and cell division of isolated CD8+CD127+ and CD8+CD127– T cells in response to common IL-2 receptor {gamma} chain ({gamma}C) cytokines other than IL-7. We show here that (i) memory cells (CD127+CD45RA–) divide frequently in response to either IL-2, -4 or -15; (ii) IL-2 and -15 enhance cell division in effector–memory-like cells (CD127–CD45RA+) while IL-4 enhances the cell division of effector cells (CD127–CD45RA–); (iii) CD8+CD127+ T cells are more sensitive to the anti-apoptotic effects of IL-2 or IL-15 than CD8+CD127– T cells and (iv) CD8+CD127+ T cell produce more Bcl-2 in response to IL-2 or IL-15 compared with CD8+CD127– T cells. Therefore, CD8+CD127+ and CD8+CD127– T cells differ in their responsiveness to cell division and anti-apoptotic signals from IL-2, -4 and -15. This suggests a role for {gamma}C cytokines in the pathogenesis of diseases in which CD127 expression is altered on CD8+ T cells such as in progressive viral infections and cancer.

Keywords: CD8+ T cells, gamma chain cytokines, IL-7 receptor

Transmitting editor: W. J. Leonard

Received 16 May 2008, accepted 4 October 2008.


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