Thymocytes can become mature T cells without passing through the CD4+ CD8+, double-positive stage.
T cells bearing the class II-restricted, DO-T cell receptor (TCR) are CD4+ if their thymocyte precursors are positively selected on the class II protein, IAd, but they are almost all CD4- after positive selection on a class II for which they have higher avidity, IAb. DO-TCR+ T cells mature in H-2b mice lacking CD4. CD4- DO-TCR+ T cells appear in H-2b mice at the same rate as their CD4+ counterparts appear in H-2d animals, suggesting that the CD4- cells are not the product of some minor pathway of thymocyte development and selection. In H-2b CD4 knock out mice expressing human CD2 under the control of the mouse CD4 promoter, mature DO-TCR+ cells did not express human CD2. These results suggest that the CD4-CD8-, DO-TCR+ mature T cells have developed without ever passing through the equivalent of a CD4+,CD8+ stage. The early expression of alpha/beta receptors (TCRs) on thymocytes in TCR transgenic mice may allow maturation of this type. Passage through the equivalent of the CD4+ CD8+, double-positive stage is not essential for differentiation of thymocytes into mature T cells.
Liu
C P
CP
Howard Hughes Medical Institute, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Kappler
J W
JW
Marrack
P
P
D000818:Animals; D015704:CD4 Antigens; D016827:CD8 Antigens / Q000235:genetics; D002454:Cell Differentiation; D002678:Chimera; D019175:DNA Methylation; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta