Abstract
The humoral immune response to most respiratory virus infections plays a prominent role in virus clearance and is essential for resistance to reinfection. T follicular helper (Tfh) cells are believed to support the development both of a potent primary antibody response and of the germinal center response critical for memory B cell development. Using a model of primary murine influenza A virus (IAV) infection, we demonstrate that a novel late activator antigen-presenting cell (LAPC) promotes the Tfh response in the draining lymph nodes (dLNs) of the IAV-infected lungs. LAPCs migrate from the infected lungs to the dLN "late," i.e., 6 d after infection, which is concomitant with Tfh differentiation. LAPC migration is CXCR3-dependent, and LAPC triggering of Tfh cell development requires ICOS-ICOSL-dependent signaling. LAPCs appear to play a pivotal role in driving Tfh differentiation of Ag-primed CD4(+) T cells and antiviral antibody responses.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology*
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Antigens / immunology*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Communication / immunology
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Cell Differentiation / immunology*
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Cell Movement / immunology
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Germinal Center / immunology
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Immunity, Humoral
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Inducible T-Cell Co-Stimulator Ligand / metabolism
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Inducible T-Cell Co-Stimulator Protein / metabolism
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Lymph Nodes / immunology
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Mice
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Mice, Knockout
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Orthomyxoviridae Infections / immunology
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Protein Binding
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Receptors, CXCR3 / metabolism
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Respirovirus Infections / immunology*
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T-Lymphocytes, Helper-Inducer / cytology*
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
Substances
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Antigens
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Inducible T-Cell Co-Stimulator Ligand
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Inducible T-Cell Co-Stimulator Protein
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Receptors, CXCR3