The Janus Face of Follicular T Helper Cells in Chronic Viral Infections

• Published in: Frontiers in immunology Vol. 9; p. 1162
• Main Authors: Greczmiel, Ute, Oxenius, Annette
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 25.05.2018
• Subjects: Animals; Antibodies, Viral - metabolism; antibody responses; Autoimmunity; B-Lymphocytes - immunology; Cell Differentiation; Chronic Disease; chronic viral infection; Cytokines - metabolism; follicular helper cells; germinal center; Germinal Center - immunology; Humans; Hypergammaglobulinemia - etiology; Hypergammaglobulinemia - immunology; Immune Tolerance; Immunity, Humoral; Immunology; Lymphocyte Activation; T-Lymphocytes, Helper-Inducer - physiology; viral evolution; Virus Diseases - complications; Virus Diseases - immunology; viral evolution; chronic viral infection; germinal center; antibody responses; follicular helper cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.01162

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 (T ) 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 T 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 T 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 T cells in chronic viral infections.