Abstract
The first checkpoint in T cell development, beta selection, has remained incompletely characterized for lack of specific surface markers. We show that CD27 is upregulated in DN3 thymocytes initiating beta selection, concomitant with intracellular TCR-beta expression. Clonal analysis determined that CD27high DN3 cells generate CD4+CD8+ progeny with more than 90% efficiency, faster and more efficiently than the CD27low majority. CD27 upregulation also occurs in gammadelta-selected DN3 thymocytes in TCR-beta-/- mice and in IL2-GFP transgenic reporter mice where GFP marks the earliest emerging TCR-gammadelta cells from DN3 thymocytes. With CD27 to distinguish pre- and postselection DN3 cells, a detailed gene expression analysis defined regulatory changes associated with checkpoint arrest, with beta selection, and with gammadelta selection. gammadelta selection induces higher CD5, Egr, and Runx3 expression as compared to beta selection, but it triggers less proliferation. Our results also reveal differences in Notch/Delta dependence at the earliest stages of divergence between developing alphabeta and gammadelta T-lineage 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 / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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Cell Lineage / genetics
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Gene Expression Profiling
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Gene Expression Regulation, Developmental
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Interleukin-2 / genetics
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / metabolism
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Mice
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Mice, Mutant Strains
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / metabolism*
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / metabolism*
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Receptors, Notch / metabolism
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Stem Cells / cytology
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Stem Cells / immunology
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Thymus Gland / cytology
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Thymus Gland / growth & development*
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Transgenes
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / analysis*
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
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Up-Regulation
Substances
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Interleukin-2
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Notch
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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delta protein