Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients
- Institut Pasteur, France
- University Pierre et Marie Curie, France
- Albert-Ludwigs-Universität, Germany
- Assistance publique - hôpitaux de Paris, France
- The Netherlands Cancer Institute, Netherlands
- Lunds University, Sweden
- Assistance publique - Hôpitaux de Paris, France
- Université Paris Descartes, France
- Assistance Publique - Hôpitaux de Paris, France
- Albert-Ludwigs-Universität Freiburg, Germany
Abstract
Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.
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Ethics
Human subjects: 29 cHCV, 37 SVR, and 18 cHBV patients were included (Table 1). All subjects were followed in the Liver Unit of H�pital Cochin (Paris, France) or the Department of Internal Medicine II (Freiburg, Germany). French samples were obtained as part of study protocol C11-33 approved by the INSERM clinical investigation department with ethical approval from the CPP Ile-de-France II, Paris (ClinicalTrials.gov identifier: n{degree sign}NCT01534728). German samples were obtained in the University Hospital Freiburg according to regulations of local ethic committee. Both study protocols conformed to the ethical guidelines of the Declaration of Helsinki, and patients provided informed consent.
Copyright
© 2015, Alanio et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients
eLife 4:e07916.
https://doi.org/10.7554/eLife.07916
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