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
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
eLife. - 4 (2015) , e07916, ISSN: 2050-084X

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2019
Urheber
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
10.7554/elife.07916
URN
urn:nbn:de:bsz:25-freidok-1279752
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.02.0025, 00:00 MEZ

Datenpartner

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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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