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.
| Original language | English |
|---|---|
| Pages (from-to) | 674-683 |
| Number of pages | 10 |
| Journal | Journal of Infectious Diseases |
| Volume | 213 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 15 2016 |
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Keywords
- apoptosis
- CD8+ T cells
- chronic immune activation
- hepatitis C virus
ASJC Scopus subject areas
- Infectious Diseases
- Immunology and Allergy
Cite this
Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic Hepatitis C virus infection. / 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.
In: Journal of Infectious Diseases, Vol. 213, No. 4, 15.02.2016, p. 674-683.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic Hepatitis C virus infection
AU - Martini, Helene
AU - Citro, Alessandra
AU - Martire, Carmela
AU - D'ettorre, Gabriella
AU - Labbadia, Giancarlo
AU - Accapezzato, Daniele
AU - Piconese, Silvia
AU - De Marzio, Paolo
AU - Cavallari, Eugenio N.
AU - Calvo, Ludovica
AU - Rizzo, Fabiana
AU - Severa, Martina
AU - Coccia, Eliana M.
AU - Grazi, Gian Luca
AU - Di Filippo, Simona
AU - Sidney, John
AU - Vullo, Vincenzo
AU - Sette, Alessandro
AU - Barnaba, Vincenzo
PY - 2016/2/15
Y1 - 2016/2/15
N2 - 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.
AB - 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.
KW - apoptosis
KW - CD8+ T cells
KW - chronic immune activation
KW - hepatitis C virus
UR - http://www.scopus.com/inward/record.url?scp=84960172560&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84960172560&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiv460
DO - 10.1093/infdis/jiv460
M3 - Article
C2 - 26386427
AN - SCOPUS:84960172560
VL - 213
SP - 674
EP - 683
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 4
ER -