Dataset Information

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-?, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection.

SUBMITTER: Franceschini D

PROVIDER: S-EPMC3380931 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Franceschini Debora D Del Porto Paola P Piconese Silvia S Trella Emanuele E Accapezzato Daniele D Paroli Marino M Morrone Stefania S Piccolella Enza E Spada Enea E Mele Alfonso A Sidney John J Sette Alessandro A Barnaba Vincenzo V

PLoS pathogens 20120621 6

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 ...[more]

PMID: 22737070

Similar Datasets

Project description:Long term carriers were shown to generate robust polyfunctional T cell (PFC) responses against lytic and latent antigens of Epstein-Barr virus (EBV). However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not clearly understood. A longitudinal study was performed to assess the development of antigen-specific PFC responses in children diagnosed to have primary symptomatic (infectious mononucleosis [IM]) and asymptomatic (AS) EBV infection. Evaluation of IFN-? secreting CD8+ T cell responses upon stimulation by HLA class I-specific peptides of EBV lytic and latent proteins by ELISPOT assay followed by assessment of CD4+ and CD8+ PFC responses upon stimulation by a panel of overlapping EBV peptides for co-expression of IFN-?, TNF-?, IL-2, perforin and CD107a by flow cytometry were performed. Cytotoxicity of T cells against autologous lymphoblastoid cell lines (LCLs) as well as EBV loads in PBMC and plasma were also determined. Both IM and AS patients had elevated PBMC and plasma viral loads which declined steadily during a 12-month period from the time of diagnosis whilst decrease in the magnitude of CD8+ T cell responses toward EBV lytic peptides in contrast to increase toward latent peptides was shown with no significant difference between those of IM and AS patients. Both lytic and latent antigen-specific CD4+ and CD8+ T cells demonstrated polyfunctionality (defined as greater or equal to three functions) concurrent with enhanced cytotoxicity against autologous LCLs and steady decrease in plasma and PBMC viral loads over time. Immunodominant peptides derived from BZLF1, BRLF1, BMLF1 and EBNA3A-C proteins induced the highest proportion of CD8+ as well as CD4+ PFC responses. Diverse functional subtypes of both CD4+ and CD8+ PFCs were shown to emerge at 6-12 months. In conclusion, EBV antigen-specific CD4+ and CD8+ PFC responses emerge during the first year of primary EBV infection, with greatest responses toward immunodominant epitopes in both lytic and latent proteins, correlating to steady decline in PBMC and plasma viral loads.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets