Abstract
The T-box transcription factor, T-bet promotes the differentiation of short-lived effector CD8(+) T cells at the expense of central memory cells. How T-bet mediates these effects, and whether they are directly caused by T-bet alone are unknown, because expression of T-bet requires stimulation of the T cell by inflammatory and growth cytokines, which may have T-bet-independent functions involving T-cell differentiation. We developed an in vitro system of ectopic T-bet expression that avoids the effects of inflammatory cytokines to determine which aspects of the T-bet phenotype may be accounted for by T-bet alone. Ectopic T-bet expression by OT-I CD8(+) T cells stimulated by the H2-Kb (SIINFEKL) complex and cultured with 2 ng/mL IL-2 induced a coordinated change in gene expression leading to down-regulation of CD127 and SOCS-1 and up-regulation of CD122 and IL-15 receptor α, switching the cellular survival cytokine from IL-7 to IL-15. T-bet expression and 2 ng/mL IL-2 also led to a capacity for IFN-γ and Fas ligand expression, confirming a role in eliciting these effector functions. Finally, ectopic T-bet promoted the expression of B lymphocyte-induced maturation protein 1 by OT-I cells in the presence of 20 ng/mL IL-2, providing a mechanism for the role of T-bet in driving terminal differentiation in concert with a high level of IL-2 receptor signalling.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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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 Survival / immunology
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Cells, Cultured
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Down-Regulation
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Fas Ligand Protein / immunology
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Fas Ligand Protein / metabolism
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Gene Expression / immunology
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-15 / immunology
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Interleukin-15 / metabolism
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Interleukin-15 Receptor alpha Subunit / analysis
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Interleukin-15 Receptor alpha Subunit / immunology
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Interleukin-2 / immunology
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Interleukin-2 / metabolism
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Interleukin-2 Receptor beta Subunit / analysis
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Interleukin-2 Receptor beta Subunit / immunology
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Interleukin-7 / immunology
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Interleukin-7 / metabolism
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Interleukin-7 Receptor alpha Subunit / immunology
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Interleukin-7 Receptor alpha Subunit / metabolism
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Lymphocyte Activation*
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Mice
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Mice, Inbred C57BL
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Positive Regulatory Domain I-Binding Factor 1
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins / immunology
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Suppressor of Cytokine Signaling Proteins / metabolism
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T-Box Domain Proteins / immunology*
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T-Box Domain Proteins / metabolism
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Transcription Factors / immunology
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Transcription Factors / metabolism
Substances
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Fas Ligand Protein
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Il2rb protein, mouse
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Interleukin-15
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Interleukin-15 Receptor alpha Subunit
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Interleukin-2
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Interleukin-2 Receptor beta Subunit
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Interleukin-7
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Interleukin-7 Receptor alpha Subunit
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Prdm1 protein, mouse
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Socs1 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Transcription Factors
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Interferon-gamma
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Positive Regulatory Domain I-Binding Factor 1