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International Immunology Advance Access originally published online on October 22, 2007
International Immunology 2007 19(12):1329-1339; doi:10.1093/intimm/dxm102
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© The Author 2007. 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-7 decreases IL-7 receptor {alpha} (CD127) expression and induces the shedding of CD127 by human CD8+ T cells

Agatha Vranjkovic1,2,*, Angela M. Crawley1,*, Katrina Gee1,3, Ashok Kumar2,3 and Jonathan B. Angel1,2,4

1 Ottawa Health Research Institute, Ottawa, Ontario, Canada
2 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada
3 Division of Virology and Molecular Immunology, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
4 Division of Infectious Diseases, Ottawa Hospital—General Campus, Ottawa, Ontario, Canada

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

IL-7 receptor {alpha} (CD127) signaling is essential for T-cell development and regulation of naive and memory T-cell homeostasis. Fewer CD8+ T cells from HIV-infected patients express CD127 compared with healthy individuals, suggesting that specific host and/or viral factors regulate IL-7 receptor expression. Factors relevant to HIV infection that could potentially decrease CD127 expression on human CD8+ T cells and the mechanisms by which this occurs were therefore evaluated. IL-7, but not HIV gp120, IL-1-ß, IL-6, IL-10, IL-13, transforming growth factor-ß or tumor necrosis factor-{alpha}, reduced CD127-surface expression and did so without altering CD127 mRNA expression. Furthermore, IL-7 did not increase the amount of cytoplasmic CD127 in CD8+ T cells. Interestingly, IL-7 induced the shedding of CD127 from CD8+ T cells, suggesting a mechanism that may contribute to the increased concentration of CD127 in the plasma of HIV+ individuals, a novel finding reported here. Naive CD8+ T cells are more sensitive to IL-7 that mediated the down-regulation of CD127, suggesting that these effects may have particular significance early in T-cell life cycle. Since CD127 down-regulation may be an important contributor to HIV-associated T-cell dysfunction, determining the mechanism thereof may prove to be of considerable significance.

Keywords: cytokines, {gamma}-chain cytokine receptors, HIV, receptor internalization, receptor secretion

* These authors contributed equally to this study.

Transmitting editor: A. Singer

Received 20 March 2007, accepted 20 September 2007.


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