PLoS pathogens, 2018-05, Vol.14 (5), p.e1007053-e1007053
2018
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- Autor(en) / Beteiligte
- Titel
- The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection
- Ist Teil von
- PLoS pathogens, 2018-05, Vol.14 (5), p.e1007053-e1007053
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- CD4 T cell-mediated help to CD8 T cells and B cells is a critical arm of the adaptive immune system required for control of pathogen infection. CD4 T cells express cytokines and co-stimulatory molecules that support a sustained CD8 T cell response and also enhance generation of protective antibody by germinal center B cells. However, the molecular components that modulate CD4 T cell functions in response to viral infection or vaccine are incompletely understood. Here we demonstrate that inactivation of the signaling adaptor CD2-associated protein (CD2AP) promotes CD4 T cell differentiation towards the follicular helper lineage, leading to enhanced control of viral infection by augmented germinal center response in chronic lymphocytic choriomeningitis virus (LCMV) infection. The enhanced follicular helper differentiation is associated with extended duration of TCR signaling and enhanced cytokine production of CD2AP-deficient CD4 T cells specifically under TH1 conditions, while neither prolonged TCR signaling nor enhanced follicular helper differentiation was observed under conditions that induce other helper effector subsets. Despite the structural similarity between CD2AP and the closely related adaptor protein CIN85, we observed defective antibody-mediated control of chronic LCMV infection in mice lacking CIN85 in T cells, suggesting non-overlapping and potentially antagonistic roles for CD2AP and CIN85. These results suggest that tuning of TCR signaling by targeting CD2AP improves protective antibody responses in viral infection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1007053Titel-ID: cdi_plos_journals_2049929976
- Format
- –
- Schlagworte
- Adaptive control, Adaptor Proteins, Signal Transducing - immunology, Adaptor Proteins, Signal Transducing - metabolism, Adaptor Proteins, Signal Transducing - physiology, Animals, Antibody Formation, Antigens, B-Lymphocytes - immunology, Biology and Life Sciences, CD2-associated protein, CD4 antigen, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - metabolism, CD4-Positive T-Lymphocytes - physiology, CD8 antigen, CD8-Positive T-Lymphocytes - immunology, Cell differentiation, Cell Differentiation - immunology, Cellular signal transduction, Chronic infection, Cytokines, Cytoskeletal Proteins - immunology, Cytoskeletal Proteins - metabolism, Cytoskeletal Proteins - physiology, Deactivation, Differentiation (biology), Germinal Center - immunology, Immune response, Immune system, Immunology, Inactivation, Infections, Laboratories, Lymphocytes, Lymphocytes B, Lymphocytes T, Lymphocytic Choriomeningitis - virology, Lymphocytic choriomeningitis virus - immunology, Lymphocytic choriomeningitis virus - pathogenicity, Medicine, Medicine and Health Sciences, Mice, Mice, Inbred C57BL, Molecular chains, Pathology, Proteins, Signal Transduction, Signaling, T cell receptors, T cells, T-cell receptor, T-Lymphocytes, Helper-Inducer - immunology, T-Lymphocytes, Helper-Inducer - metabolism, T-Lymphocytes, Helper-Inducer - physiology, Viral infections, Viral meningitis, Viruses