Article abstract
Nature Immunology 8, 1049 - 1059 (2007)
Published online: 16 September 2007 | doi:10.1038/ni1512
'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR
Jung-Hyun Park1, Stanley Adoro1,2, Philip J Lucas3, Sophia D Sarafova1,8, Amala S Alag1, Loretta L Doan1, Batu Erman4, Xiaolong Liu5, Wilfried Ellmeier6, Remy Bosselut5, Lionel Feigenbaum7 & Alfred Singer1
Abstract
T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR). 'Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common 
-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR engagement of self ligands, whereas TCR signals impair common -chain cytokine signaling and thereby decrease CD8 expression. This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity.
- Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Immunology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
- Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
- Immune Cell Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Institute of Immunology, Medical University of Vienna, Vienna, Austria.
- SAIC-Frederick, National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
- Present address: Biology Department, Davidson College, Davidson, North Carolina 28035, USA.
Correspondence to: Alfred Singer1 e-mail: singera@nih.gov
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