title: Apoptotic Epitope-Specific CD8+ T Cells and Interferon Signaling Intersect in Chronic Hepatitis C Virus Infection.
abstract: CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation. Here, we found that both apoptotic epitope-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper 1-like signature program in chronic HCV infection. However, apoptotic epitope-specific CD8(+) T cells produced tumor necrosis factor α and interleukin 2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations expressing high levels of programmed death 1 receptor. Contextually, only apoptotic epitope-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Together, these data suggest that, compared with HCV-specific CD8(+) T cells, apoptotic epitope-specific CD8(+) T cells can better sustain chronic immune activation, owing to their capacity to produce tumor necrosis factor α, and exhibit greater resistance to inhibitory signals during chronic HCV infection.
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Helene
authors.initials: H
authors.lastname: Martini
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Citro
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Carmela
authors.initials: C
authors.lastname: Martire
authors.affiliation: Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Ettorre
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Labbadia
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Daniele
authors.initials: D
authors.lastname: Accapezzato
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Silvia
authors.initials: S
authors.lastname: Piconese
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Marzio
authors.affiliation: Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma.
authors.forename: Eugenio N
authors.initials: EN
authors.lastname: Cavallari
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Calvo
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rizzo
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità
authors.forename: Martina
authors.initials: M
authors.lastname: Severa
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità
authors.forename: Eliana M
authors.initials: EM
authors.lastname: Coccia
authors.affiliation: Chirurgia Epato-bilio-pancreatica, Istituto Nazionale dei Tumori Regina Elena.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Grazi
authors.affiliation: Chirurgia Epato-bilio-pancreatica, Istituto Nazionale dei Tumori Regina Elena.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Filippo
authors.affiliation: La Jolla Institute for Allergy and Immunology, San Diego, California.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.affiliation: La Jolla Institute for Allergy and Immunology, San Diego, California.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons
keywords: CD8+ T cells; apoptosis; chronic immune activation; hepatitis C virus