Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic Hepatitis C virus infection
Autor: | Daniele Accapezzato, Paolo De Marzio, Giancarlo Labbadia, Vincenzo Vullo, Simona Di Filippo, Gabriella d'Ettorre, Martina Severa, Eugenio Nelson Cavallari, Silvia Piconese, Vincenzo Barnaba, Helene Martini, Eliana M. Coccia, Alessandra Citro, Carmela Martire, G. Grazi, John Sidney, Fabiana Rizzo, Alessandro Sette, Ludovica Calvo |
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Přispěvatelé: | Martini, Helene, Citro, Alessandra, Martire, Carmela, D'Ettorre, Gabriella, Labbadia, Giancarlo, Accapezzato, Daniele, Piconese, Silvia, De Marzio, Paolo, Cavallari, Eugenio N., Calvo, Ludovica, Rizzo, Fabiana, Severa, Martina, Coccia, Eliana M., Grazi, Gian Luca, Di Filippo, Simona, Sidney, John, Vullo, Vincenzo, Sette, Alessandro, Barnaba, Vincenzo |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Liver Cirrhosis
0301 basic medicine Adult Male Liver Cirrhosi Apoptosis T-Lymphocyte Subset Infectious Disease CD8-Positive T-Lymphocytes Biology 03 medical and health sciences Interleukin 21 T-Lymphocyte Subsets Humans Cytotoxic T cell hepatitis C viru Immunology and Allergy IL-2 receptor Antigen-presenting cell Interleukin 3 Aged chronic immune activation Tumor Necrosis Factor-alpha ZAP70 Medicine (all) Apoptosi CD8-Positive T-Lymphocyte Hepatitis C Chronic Middle Aged Natural killer T cell 030104 developmental biology Infectious Diseases Immunology Interleukin 12 Cancer research Interferon Interleukin-2 Female Interferons CD8+ T cell Human Signal Transduction |
Popis: | 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 A± 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 A±, and exhibit greater resistance to inhibitory signals during chronic HCV infection. |
Databáze: | OpenAIRE |
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