Another view of the selective model of thymocyte selection.
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.
Chan
S H
SH
Laboratoire de Génétique Moléculaire, Eucaryotes du Centre National de la Recherche Scientifique, Faculté de Médecine, Strasbourg, France.
Cosgrove
D
D
Waltzinger
C
C
Benoist
C
C
Mathis
D
D
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D018398:Homeodomain Proteins; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011506:Proteins / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein; D015759:Ionomycin; D004247:DNA; D004253:DNA Nucleotidylexotransferase; D001973:Bromodeoxyuridine; D013755:Tetradecanoylphorbol Acetate