Abstract
TCR-beta gene rearrangement or expression is necessary and sufficient for the progression of early alpha beta thymocyte differentiation from the CD3-CD4-CD8- triple negative (TN)3 to the CD4+CD8+ double positive stage. The onset of TCR-beta rearrangement is currently thought to occur gradually. Some thymocytes were reported to be rearranged at the earliest (CD44+CD25-) TN stage, whereas other thymocytes did not initiate TCR-beta rearrangement until the latest (CD44-CD25-) TN stage. Here, we have isolated subsets of TN thymocytes on the basis of surface expression of CD44 and CD25, with c-kit as an additional marker. We present a revised model of early T cell development in which TCR-beta and TCR-gamma rearrangements occur abruptly, at the CD44lowCD25+ c-kitlowTN stage. A high level of c-kit expression defines pro-T cells which have not yet rearranged their TCR genes. Germ-line TCR-beta transcripts, and transcripts of recombination activating genes (RAG)-1 and 2, are detected before TCR-beta gene rearrangement. Analyses of TN thymocytes of RAG-1 mutant mice, and of various TCR mutant and TCR transgenic RAG-1 mutant mice, indicate the existence of a control point at the CD44-CD25+TN stage at which cells expressing a productively rearranged TCR-beta chain are selected for further differentiation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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CD3 Complex / analysis
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CD4 Antigens / analysis
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CD8 Antigens / analysis
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Carrier Proteins / analysis
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DNA-Binding Proteins*
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
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Homeodomain Proteins*
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Hyaluronan Receptors
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Molecular Sequence Data
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Proteins / analysis
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Proto-Oncogene Proteins / analysis
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Proto-Oncogene Proteins c-kit
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Receptor Protein-Tyrosine Kinases / analysis
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Receptors, Antigen, T-Cell, alpha-beta / physiology*
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Receptors, Antigen, T-Cell, gamma-delta / analysis
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Receptors, Cell Surface / analysis
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Receptors, Colony-Stimulating Factor / analysis
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Receptors, Lymphocyte Homing / analysis
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / physiology*
Substances
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CD3 Complex
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CD4 Antigens
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CD8 Antigens
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Carrier Proteins
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DNA-Binding Proteins
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Homeodomain Proteins
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Hyaluronan Receptors
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Proteins
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Proto-Oncogene Proteins
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Rag2 protein, mouse
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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, Cell Surface
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Receptors, Colony-Stimulating Factor
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Receptors, Lymphocyte Homing
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V(D)J recombination activating protein 2
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RAG-1 protein
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Proto-Oncogene Proteins c-kit
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Receptor Protein-Tyrosine Kinases