Abstract
Toll-like receptor (TLR) ligands are notable for their ability to induce APC maturation, which in turn facilitates optimal T cell mediated immune responses. Toll-like receptor ligands, such as CpG DNA, can also modulate immune responses by blocking the suppressive effects of CD4+CD25+ regulatory T cells (Tregs). Recently, we have demonstrated that CpG DNA, in addition to its actions on APCs and Tregs, can provide direct costimulatory signals to CD4+CD25- T cells. Here we show that this costimulatory effect is sufficient to abrogate suppression by Tregs. These data indicate a previously undefined role for TLR ligands in directly modulating CD4+ T cell responses.
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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Adjuvants, Immunologic / pharmacology
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Animals
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Antigen-Presenting Cells / immunology
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Proliferation / drug effects
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Coculture Techniques
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Forkhead Transcription Factors / metabolism
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Immune Tolerance / drug effects
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Immune Tolerance / immunology
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Interleukin-2 / metabolism
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Interleukin-2 / pharmacology
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Interleukin-2 Receptor alpha Subunit / analysis
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Differentiation Factor 88 / deficiency
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Myeloid Differentiation Factor 88 / genetics
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Myeloid Differentiation Factor 88 / physiology*
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Oligodeoxyribonucleotides / pharmacology*
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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
Substances
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Adjuvants, Immunologic
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CPG-oligonucleotide
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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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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Oligodeoxyribonucleotides