Polyfunctional type-1, -2, and -17 CD8⁺ T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection.
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.
Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
Debora
D
Franceschini
Paola
P
Del Porto
Silvia
S
Piconese
Emanuele
E
Trella
Daniele
D
Accapezzato
Marino
M
Paroli
Stefania
S
Morrone
Enza
E
Piccolella
Enea
E
Spada
Alfonso
A
Mele
John
J
Sidney
Alessandro
A
Sette
Vincenzo
V
Barnaba
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte