Abstract
Thymocyte commitment to the CD4 helper versus CD8 cytotoxic lineage has not been satisfactorily established. Two models have been elaborated: one based on instruction, the other on selection. Most previous results support the instructive model, but our comparison of thymocyte differentiation in MHC class II-, class I- and double-deficient mice provides data challenging it. There exists a significant population of CD4 single positive cells in class II-deficient animals that is intermediate in maturity between CD4+CD8+ and end-stage CD4+CD8- thymocytes and is selected on class I molecules; an equivalent CD8+CD4- population occurs in class I-deficient animals. We propose a selective model entailing two TCR-MHC molecule engagements: the first provokes random down-modulation of either CD4 or CD8 and a degree of differentiation; the second, requiring participation of the appropriate coreceptor, permits end-stage differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation, T-Lymphocyte / analysis
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Base Sequence
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Bromodeoxyuridine / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD8 Antigens / analysis
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Cell Differentiation
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Cell Division
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DNA / biosynthesis
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DNA Nucleotidylexotransferase / metabolism
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Flow Cytometry
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Histocompatibility Antigens Class I / physiology
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Histocompatibility Antigens Class II / genetics*
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Homeodomain Proteins*
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Ionomycin / pharmacology
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Mice
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Mice, Mutant Strains
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Molecular Sequence Data
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Oligodeoxyribonucleotides / chemistry
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Proteins / genetics
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocyte Subsets / cytology*
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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Helper-Inducer / cytology
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Tetradecanoylphorbol Acetate / pharmacology
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Thymus Gland / cytology*
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Thymus Gland / embryology
Substances
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Antigens, Differentiation, T-Lymphocyte
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CD8 Antigens
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Homeodomain Proteins
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Oligodeoxyribonucleotides
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Proteins
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Receptors, Antigen, T-Cell
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RAG-1 protein
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Ionomycin
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DNA
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DNA Nucleotidylexotransferase
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Bromodeoxyuridine
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Tetradecanoylphorbol Acetate