Abstract
The transcription factor Runx1 has essential roles throughout hematopoiesis. Here, we demonstrate that Runx1 is critical for T cell maturation. Peripheral naïve CD4(+) T cells from CD4-cre Runx1 cKO mice are phenotypically and functionally immature as shown by decreased production of TNF-α upon TCR stimulation. The loss of peripheral CD4(+) T cells in CD4-cre Runx1 cKO mice is not due to defects in homeostasis or decreased expression of IL-7Rα, as transgenic expression of IL-7Rα does not rescue the loss of CD4(+) T cells. Rather, immature Runx1-deficient CD4(+) T cells are eliminated in the periphery by the activation and fixation of the classical complement pathway. In the thymus, there is a severe block in all aspects of intrathymic T cell maturation, although both positive and negative selection are unaltered. Thus, loss of Runx1 leads to the earliest characterized block in post-positive selection intrathymic maturation of CD4 T cells.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / physiology*
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Cell Differentiation / genetics
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Cell Differentiation / physiology*
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Cells, Cultured
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Complement Pathway, Classical / physiology
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Complement System Proteins / metabolism
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Core Binding Factor Alpha 2 Subunit / genetics
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Core Binding Factor Alpha 2 Subunit / metabolism
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Core Binding Factor Alpha 2 Subunit / physiology*
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Flow Cytometry
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Glycosylation
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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N-Acetylneuraminic Acid / metabolism
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Receptors, Interleukin-7 / genetics
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Receptors, Interleukin-7 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / physiology*
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Thymocytes / cytology
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Thymocytes / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Core Binding Factor Alpha 2 Subunit
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Receptors, Interleukin-7
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Runx1 protein, mouse
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Tumor Necrosis Factor-alpha
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interleukin-7 receptor, alpha chain
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Complement System Proteins
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N-Acetylneuraminic Acid