A timely, efficient, and coordinated activation of both CD4 and CD8 T cell subsets following HCV infection is believed to be essential for HCV control. However, to what extent a failure of the individual T cell subsets can contribute to the high propensity of HCV to persist is still largely undefined. To address this issue, we analyzed the breadth, vigor, and quality of CD4 and CD8 responses simultaneously with panels of peptides covering the entire HCV sequence or containing the HLA-A2-binding motif, and with recombinant HCV proteins in 16 patients with acute HCV infection by tetramer staining, ELISPOT, and intracellular cytokine staining for interferon γ, interleukin (IL)-2, IL-4, and IL-10. Our results indicate that at clinical onset, CDS responses are similarly weak and narrowly focused in both self-limited and chronically evolving infections. At this stage, CD4 responses are deeply impaired in patients with a chronic outcome as they are weak and of narrow specificity, unlike the strong, broad and T helper 1-oriented CD4 responses associated with resolving infections. Only patients able to finally control infection show maturation of CD8 memory sustained by progressive expansion of CD127+ CD8 cells. Thus, a poor CD8 response in the acute stage of infection may enhance the overall probability of chronic viral persistence. In conclusion, the presence of functional CD4 responses represents one of the factors dictating the fate of infection by directly contributing to control of the virus and by promoting maturation of protective memory CD8 responses. Copyright © 2006 by the American Association for the Study of Liver Diseases.

Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses / Urbani, Simona; Amadei, Barbara; Fisicaro, Paola; Tola, Daniela; Orlandini, Alessandra; Sacchelli, Luca; Mori, Cristina; Missale, Gabriele; Ferrari, Carlo. - In: HEPATOLOGY. - ISSN 0270-9139. - 44:1(2006), pp. 126-139. [10.1002/hep.21242]

Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses

Missale, Gabriele;FERRARI, Carlo
2006-01-01

Abstract

A timely, efficient, and coordinated activation of both CD4 and CD8 T cell subsets following HCV infection is believed to be essential for HCV control. However, to what extent a failure of the individual T cell subsets can contribute to the high propensity of HCV to persist is still largely undefined. To address this issue, we analyzed the breadth, vigor, and quality of CD4 and CD8 responses simultaneously with panels of peptides covering the entire HCV sequence or containing the HLA-A2-binding motif, and with recombinant HCV proteins in 16 patients with acute HCV infection by tetramer staining, ELISPOT, and intracellular cytokine staining for interferon γ, interleukin (IL)-2, IL-4, and IL-10. Our results indicate that at clinical onset, CDS responses are similarly weak and narrowly focused in both self-limited and chronically evolving infections. At this stage, CD4 responses are deeply impaired in patients with a chronic outcome as they are weak and of narrow specificity, unlike the strong, broad and T helper 1-oriented CD4 responses associated with resolving infections. Only patients able to finally control infection show maturation of CD8 memory sustained by progressive expansion of CD127+ CD8 cells. Thus, a poor CD8 response in the acute stage of infection may enhance the overall probability of chronic viral persistence. In conclusion, the presence of functional CD4 responses represents one of the factors dictating the fate of infection by directly contributing to control of the virus and by promoting maturation of protective memory CD8 responses. Copyright © 2006 by the American Association for the Study of Liver Diseases.
2006
Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses / Urbani, Simona; Amadei, Barbara; Fisicaro, Paola; Tola, Daniela; Orlandini, Alessandra; Sacchelli, Luca; Mori, Cristina; Missale, Gabriele; Ferrari, Carlo. - In: HEPATOLOGY. - ISSN 0270-9139. - 44:1(2006), pp. 126-139. [10.1002/hep.21242]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2814931
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