Abstract
In OVA-sensitized and challenged mice, gammadelta T cells expressing Vgamma1 enhance airway hyperresponsiveness (AHR) but the underlying mechanism is unclear. These cells also reduce IL-10 levels in the airways, suggesting that they might function by inhibiting CD4(+)CD25(+) regulatory T cells (T(reg)) or other CD4(+) T cells capable of producing IL-10 and suppressing AHR. Indeed, sensitization and challenge with OVA combined with inactivation of Vgamma1(+) cells increased CD4(+)CD25(+) cells in the lung, and markedly those capable of producing IL-10. The cellular change was associated with increased IL-10 and TGF-beta levels in the airways, and a decrease of IL-13. T(reg) include naturally occurring Foxp3(+) T(reg), inducible Foxp3(-) T(reg), and antigen-specific T(reg) many of which express folate receptor 4 (FR4). Although Foxp3 gene expression in the lung was also increased pulmonary CD4(+) T cells, expressing Foxp3-protein or FR4 remained stable. Therefore, the inhibition by Vgamma1(+) gammadelta T cells might not be targeting Foxp3(+) T(reg) but rather CD4(+) T cells destined to produce IL-10.
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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Aluminum Hydroxide / administration & dosage
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Animals
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Antibodies, Blocking / administration & dosage
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Antibodies, Blocking / immunology
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CD4 Antigens / biosynthesis
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Female
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Folate Receptors, GPI-Anchored
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Genes, T-Cell Receptor gamma / immunology
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Interleukin-10 / metabolism*
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Interleukin-13 / metabolism
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Interleukin-2 Receptor alpha Subunit / biosynthesis
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Lung / pathology
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Mice
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Mice, Inbred C57BL
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Ovalbumin / administration & dosage
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Receptors, Antigen, T-Cell, gamma-delta / immunology
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Receptors, Antigen, T-Cell, gamma-delta / metabolism*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism
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Respiratory Hypersensitivity / immunology
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Respiratory Hypersensitivity / metabolism*
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Respiratory Hypersensitivity / pathology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / pathology
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Transforming Growth Factor beta / metabolism
Substances
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Antibodies, Blocking
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CD4 Antigens
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Carrier Proteins
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FOXP3 protein, human
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Folate Receptors, GPI-Anchored
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Forkhead Transcription Factors
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Interleukin-13
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Interleukin-2 Receptor alpha Subunit
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Cell Surface
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Transforming Growth Factor beta
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folate receptor 4, mouse
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Interleukin-10
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Aluminum Hydroxide
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Ovalbumin