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Elife. 2015 Nov 14;4. pii: e07916. doi: 10.7554/eLife.07916.

Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients.

Author information

1
Unités de Recherche Internationales Mixtes Pasteur, Institut Pasteur, Paris, France.
2
Centre d'Immunologie Humaine, Institut Pasteur, Paris, France.
3
Immunobiology of Dendritic Cells, Institut Pasteur, Paris, France.
4
Sorbonne Universités, UPMC Univ Paris 06, DNU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
5
Emory, , United States.
6
The University Medical Center Freiburg, Department of Internal Medicine II, Albert-Ludwigs-Universität, Freiberg, Germany.
7
Immunoregulation Unit, Institut Pasteur, Paris, France.
8
Plateforme d'Immunoscope, Institut Pasteur, Paris, France.
9
Hôpital Saint-Louis, Assistance publique - hôpitaux de Paris, Paris, France.
10
Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
11
Laboratoire de virologie, Hôpital Armand-Trousseau, Assistance publique - hôpitaux de Paris, Paris, France.
12
Mathematics, Faculty of Engineering, Lunds University, Lund, Sweden.
13
APHP, Université Paris Descartes, Paris, France.
14
EFS, Hôpital Cochin, Paris, France.

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.

KEYWORDS:

CD8 T cell dysfunction; Pre-immune repertoire; TCR signaling; chronic inflammation; human; human biology; immunology; medicine; viral immunology

PMID:
26568315
PMCID:
PMC4752008
DOI:
10.7554/eLife.07916
[Indexed for MEDLINE]
Free PMC Article

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