
Open access
Date
2018-05-25Type
- Review Article
Citations
Cited 11 times in
Web of Science
Cited 11 times in
Scopus
ETH Bibliography
yes
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Abstract
Chronic infections with non-cytopathic viruses constitutively expose virus-specific adaptive immune cells to cognate antigen, requiring their numeric and functional adaptation. Virus-specific CD8 T cells are compromised by various means in their effector functions, collectively termed T cell exhaustion. Alike CD8 T cells, virus-specific CD4 Th1 cell responses are gradually downregulated but instead, follicular T helper (TFH) cell differentiation and maintenance is strongly promoted during chronic infection. Thereby, the immune system promotes antibody responses, which bear less immune-pathological risk compared to cytotoxic and pro-inflammatory T cell responses. This emphasis on TFH cells contributes to tolerance of the chronic infection and is pivotal for the continued maturation and adaptation of the antibody response, leading eventually to the emergence of virus-neutralizing antibodies, which possess the potential to control the established chronic infection. However, sustained high levels of TFH cells can also result in a less stringent B cell selection process in active germinal center reactions, leading to the activation of virus-unspecific B cells, including self-reactive B cells, and to hypergammaglobulinemia. This dispersal of B cell help comes at the expense of a stringently selected virus-specific antibody response, thereby contributing to its delayed maturation. Here, we discuss these opposing facets of TFH cells in chronic viral infections. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000268287Publication status
publishedExternal links
Journal / series
Frontiers in ImmunologyVolume
Pages / Article No.
Publisher
Frontiers Research FoundationSubject
follicular helper cells; chronic viral infection; antibody responses; germinal center; viral evolutionOrganisational unit
03625 - Oxenius, Annette / Oxenius, Annette
Funding
146140 - Regulation of adaptive immunity during acute and persistent viral infections (SNF)
166078 - Antibody evolution during chronic viral infections: a functional and systems immunological approach (SNF)
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Show all metadata
Citations
Cited 11 times in
Web of Science
Cited 11 times in
Scopus
ETH Bibliography
yes
Altmetrics