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

Debora Franceschini (1) , Paola del Porto (2) , Silvia Piconese (1) , Emanuele Trella (1) , Daniele Accapezzato (1) , Marino Paroli (3) , Stefania Morrone (4) , Enza Piccolella (2) , Enea Spada (5) , Alfonso Mele (6) , John Sidney (6) , Alessandro Sette (7) , Vincenzo Barnaba (1, 8, 9)

1 Department of Internal Medicine and Medical Specialities
2 Department of Biology and Biotechnology "Charles Darwin"
3 Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche
4 Department of Molecular Medicine
5 CNESPS - National Centre for Epidemiology, Surveillance and Health Promotion = Centro nazionale di epidemiologia, sorveglianza e promozione della salute
6 Laboratory of Epidemiology, Clinical Epidemiology Unit
7 La Jolla Institute for Immunology [La Jolla, CA, États-Unis]
8 Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti
9 Fondazione Andrea Cesalpino

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.

Domaines: Immunologie; Virologie

Debora Franceschini, Paola del Porto, Silvia Piconese, Emanuele Trella, Daniele Accapezzato, et al.. Polyfunctional type-1, -2, and -17 CD8⁺ T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection.. PLoS Pathogens, 2012, 8 (6), pp.e1002759. ⟨10.1371/journal.ppat.1002759⟩. ⟨pasteur-00966408⟩