Abstract
Mutually exclusive cell fate determination of CD4 helper or CD8 killer T cells occurs in the thymus. These T-cell subsets are not believed to redirect other lineages. Here we showed that retinoic acid and transforming growth factor-β1 promoted the differentiation of CD8αα T cells from CD4 T cells in a Runx3-dependent manner. These cells were inferred to belong to immunoregulatory populations because subpopulations of CD8αα+TCRαβ T cells are known to suppress activated T cells, and mice with Runx3(-/-) T cells showed defects during recovery from experimental allergic encephalomyelitis. Our results demonstrate that CD4 T cells play fundamental roles in controlling immune reactions through promotion and attenuation. We accordingly anticipate that clarifying the mechanisms underlying this process will provide insights leading to autoimmune and immunodeficiency disease therapies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / physiology
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CD4-Positive T-Lymphocytes / transplantation
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Differentiation*
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Cell Separation
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Cells, Cultured
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Core Binding Factor Alpha 3 Subunit / metabolism
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Core Binding Factor Alpha 3 Subunit / physiology
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Cytokines / physiology
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DNA-Binding Proteins / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Flow Cytometry
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Lymphoid Tissue / immunology
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Lymphoid Tissue / pathology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell / metabolism*
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Spleen / immunology
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Spleen / pathology
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T-Lymphocytes, Regulatory / metabolism
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Transcriptome
Substances
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Core Binding Factor Alpha 3 Subunit
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Cytokines
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DNA-Binding Proteins
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell
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Runx3 protein, mouse