Production, selection, and maturation of thymocytes with high surface density of TCR.
The main steps in intrathymic T cell differentiation have been defined using bromodeoxyuridine as a postmitotic cell tracer. Thymocytes with a high surface expression of the TCR are generated in the first 24 h after DNA synthesis. The phenotype of these TCR(high) cells was studied during 10 days by using pairs of surface markers associated with BrdUrd. During the first 2 days, TCR(high) cells were of the CD4+CD8+HSA(high) phenotype, transiently expressed the early activation marker CD69, and contained a high percentage of cycling cells. This activation step preceded the transition from CD4+CD8+ to CD4+CD8- and then to CD4-CD8+ cells, followed by progressive HSA down regulation and increase in the expression of H-2K, Qa-2, and CD45RB. The phenotypic maturation was completed in 9 days. In Mls-1a mice, negative selection of V beta 6+ cells was observed at the earliest step of TCR(high) cell generation, and positive selection of V beta 8.2+ and V beta 14+ cells took place later and was correlated to the activation step. These data suggest that high TCR expression and cell activation are necessary for positive selection and subsequent T cell maturation.
Lucas
B
B
U.345 INSERM, CHU Necker-enfants Malades, Paris, France.
Vasseur
F
F
Penit
C
C
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D002454:Cell Differentiation; D002469:Cell Separation; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C032907:Q surface antigens