Abstract
To explore the interactions between regulatory T cells and pathogenic effector cytokines, we have developed a model of a T cell-mediated systemic autoimmune disorder resembling graft-versus-host disease. The cytokine responsible for tissue inflammation in this disorder is interleukin (IL)-17, whereas interferon (IFN)-gamma produced by Th1 cells has a protective effect in this setting. Because of the interest in potential therapeutic approaches utilizing transfer of regulatory T cells and inhibition of the IL-2 pathway, we have explored the roles of these in the systemic disease. We demonstrate that the production of IL-17 and tissue infiltration by IL-17-producing cells occur and are even enhanced in the absence of IL-2. Regulatory T cells favor IL-17 production but prevent the disease when administered early in the course by suppressing expansion of T cells. Thus, the pathogenic or protective effects of cytokines and the therapeutic capacity of regulatory T cells are crucially dependent on the timing and the nature of the disease.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Alopecia / immunology
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Alopecia / pathology
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Animals
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / metabolism
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Autoimmune Diseases / therapy
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Body Weight / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / transplantation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Disease Models, Animal
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Female
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Graft vs Host Disease / immunology
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Inflammation / immunology
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Inflammation / pathology
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukin-17 / metabolism
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Interleukin-17 / physiology*
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Interleukin-4 / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Transgenic
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Ovalbumin / genetics
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Ovalbumin / immunology
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Skin / immunology
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Skin / pathology
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / metabolism
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / transplantation
Substances
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DNA-Binding Proteins
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Interleukin-17
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Interleukin-2
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Rag2 protein, mouse
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Interleukin-4
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Interferon-gamma
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Ovalbumin