Abstract
Interleukin 2 (IL-2) promotes Foxp3+ regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some Treg cells downregulated CD25, upregulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones. Thus, unlike its effects on conventional Treg cells, IL-2 inhibits TFR cell responses.
MeSH terms
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Animals
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Cell Movement / genetics
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Cell Movement / immunology
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology
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Forkhead Transcription Factors / metabolism
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Gene Expression Profiling / methods
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Host-Pathogen Interactions / drug effects
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Host-Pathogen Interactions / immunology
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Interleukin-2 / administration & dosage
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Interleukin-2 / metabolism
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Interleukin-2 / pharmacology*
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Interleukin-2 Receptor alpha Subunit / genetics
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Interleukin-2 Receptor alpha Subunit / metabolism
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Orthomyxoviridae / immunology*
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Orthomyxoviridae / physiology
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Orthomyxoviridae Infections / immunology*
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Orthomyxoviridae Infections / metabolism
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Orthomyxoviridae Infections / virology
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins c-bcl-6 / genetics
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Proto-Oncogene Proteins c-bcl-6 / metabolism
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T-Lymphocytes, Helper-Inducer / drug effects*
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Regulatory / drug effects*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Transcription Factors / genetics
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Transcription Factors / immunology
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Transcription Factors / metabolism
Substances
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Prdm1 protein, mouse
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Proto-Oncogene Proteins c-bcl-6
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Transcription Factors
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Positive Regulatory Domain I-Binding Factor 1