Polyfunctional type-1, -2, and -17 CD8⁺ T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection.

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.

• Authors: Debora Franceschini, Paola Del Porto, Silvia Piconese, Emanuele Trella, Daniele Accapezzato, Marino Paroli, Stefania Morrone, Enza Piccolella, Enea Spada, Alfonso Mele, John Sidney, Alessandro Sette, Vincenzo Barnaba
• Journal: PLoS pathogens (PLoS Pathog) Vol. 8 Issue 6 Pg. e1002759 ( 2012) ISSN: 1553-7374 [Electronic] United States
• PMID: 22737070 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Epitopes, T-Lymphocyte

Topics

• Adult
• Apoptosis (immunology)
• Autoantigens (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Disease Progression
• Epitopes, T-Lymphocyte (immunology)
• Female
• Hepacivirus (immunology)
• Hepatitis C (immunology)
• Humans
• Male
• Middle Aged
• T-Lymphocyte Subsets (immunology)
• Young Adult