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- Title
Polyfunctional Type-1, -2, and -17 CD8<sup>+</sup> T Cell Responses to Apoptotic Self-Antigens Correlate with the Chronic Evolution of Hepatitis C Virus Infection.
- Authors
Franceschini, Debora; Del Porto, Paola; Piconese, Silvia; Trella, Emanuele; Accapezzato, Daniele; Paroli, Marino; Morrone, Stefania; Piccolella, Enza; Spada, Enea; Mele, Alfonso; Sidney, John; Sette, Alessandro; Barnaba, Vincenzo
- Abstract
Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8+ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8+ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8+ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection.
- Subjects
SCISSION (Chemistry); CASPASES; ANTIGENS; APOPTOSIS; CD8 antigen; T cells; HEPATITIS C virus; CYTOKINES
- Publication
PLoS Pathogens, 2012, Vol 8, Issue 6, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1002759