Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients
Abstract: Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naı ̈ve 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 naı ̈ve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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eLife. - 4 (2015) , e07916, ISSN: 2050-084X
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
-
Universität
- (wann)
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2019
- Urheber
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Alanio, Cécile
Nicoli, Francesco
Sultanik, Philippe
Flecken, Tobias
Perot, Brieuc
Duffy, Darragh
Bianchi, Elisabetta
Lim, Annick
Clave, Emmanuel
Buuren, Marit M. van
Schnuriger, Aurélie
Johnsson, Kerstin
Boussier, Jeremy
Garbarg-Chenon, Antoine
Bousquet, Laurence
Mottez, Estelle
Schumacher, Ton N.
Toubert, Antoine
Appay, Victor
Heshmati, Farhad
Thimme, Robert
Pol, Stanislas
Mallet, Vincent
Albert, Matthew L.
- Beteiligte Personen und Organisationen
- DOI
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10.7554/elife.07916
- URN
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urn:nbn:de:bsz:25-freidok-1279752
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:27 MESZ
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Beteiligte
- Alanio, Cécile
- Nicoli, Francesco
- Sultanik, Philippe
- Flecken, Tobias
- Perot, Brieuc
- Duffy, Darragh
- Bianchi, Elisabetta
- Lim, Annick
- Clave, Emmanuel
- Buuren, Marit M. van
- Schnuriger, Aurélie
- Johnsson, Kerstin
- Boussier, Jeremy
- Garbarg-Chenon, Antoine
- Bousquet, Laurence
- Mottez, Estelle
- Schumacher, Ton N.
- Toubert, Antoine
- Appay, Victor
- Heshmati, Farhad
- Thimme, Robert
- Pol, Stanislas
- Mallet, Vincent
- Albert, Matthew L.
- Universitätsklinikum Freiburg. Klinik für Innere Medizin II
- Universität
Entstanden
- 2019
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