Abstract
The role of anergy, an acquired state of T cell functional unresponsiveness, in natural peripheral tolerance remains unclear. In this study, we found that anergy was selectively induced in fetal antigen-specific maternal CD4(+) T cells during pregnancy. A naturally occurring subpopulation of anergic polyclonal CD4(+) T cells, enriched for self antigen-specific T cell antigen receptors, was also present in healthy hosts. Neuropilin-1 expression in anergic conventional CD4(+) T cells was associated with hypomethylation of genes related to thymic regulatory T cells (Treg cells), and this correlated with their ability to differentiate into Foxp3(+) Treg cells that suppressed immunopathology. Thus, our data suggest that not only is anergy induction important in preventing autoimmunity but also it generates the precursors for peripheral Treg cell differentiation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Arthritis, Experimental / immunology
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Autoimmunity / immunology*
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CD4-Positive T-Lymphocytes / immunology
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Cell Differentiation / immunology*
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Cell Proliferation
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Clonal Anergy / immunology*
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Cytokines / immunology
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Enzyme-Linked Immunosorbent Assay
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Female
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Flow Cytometry
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Forkhead Transcription Factors / immunology
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Genes, T-Cell Receptor alpha
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Histocompatibility, Maternal-Fetal / immunology*
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Immunoblotting
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Male
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Mice
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Mice, Knockout
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Neuropilin-1 / metabolism
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Peripheral Tolerance / immunology*
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Precursor Cells, T-Lymphoid / immunology*
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Pregnancy
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Receptors, Antigen, T-Cell / immunology
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Reverse Transcriptase Polymerase Chain Reaction
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Self Tolerance
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T-Lymphocytes, Regulatory / immunology*
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Thymocytes / immunology
Substances
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Cytokines
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Receptors, Antigen, T-Cell
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Neuropilin-1