Abstract
Opposite effects of common γ-chain cytokines (IL-2, IL-7, and IL-15) on the expression of Gfi1 and U2af1l4 genes regulating alternative splicing of Ptprc gene in T cells at different stages of differentiation were demonstrated in vitro. Generally, produced a dose-dependent activating effect on T cells, while to the effects of rIL-7 and rIL-15 on T cells at different stages of differentiation were opposite to that of rIL-2: maximum concentrations of recombinant cytokines IL-7 and IL-15 produced the most pronounced inhibitory effect on U2af1l4 and to a lesser extent on Gfi1 gene expression, thus limiting activation of resting cells. This is consistent with their biological effects on T cells. In general, common γ-chain cytokines IL-2, IL-7, and IL-15 prevent differentiation of naïve T cells in vitro and limit activation of primed T cells in the absence of antigenic stimulus, which can contribute to the formation of cytokine imbalance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Alternative Splicing / drug effects*
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Cell Differentiation / immunology*
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Cytokines / pharmacology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dose-Response Relationship, Drug
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Female
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Flow Cytometry
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology*
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Humans
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Immunomagnetic Separation
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Interleukin-15 / pharmacology
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Interleukin-2 / pharmacology
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Interleukin-7 / pharmacology
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Leukocyte Common Antigens / genetics
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Male
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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Splicing Factor U2AF
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Statistics, Nonparametric
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Cytokines
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DNA-Binding Proteins
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GFI1 protein, human
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Interleukin-15
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Interleukin-2
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Interleukin-7
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Nuclear Proteins
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Ribonucleoproteins
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Splicing Factor U2AF
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Transcription Factors
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U2AF1L4 protein, human
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Leukocyte Common Antigens
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PTPRC protein, human