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 TI protein, IA(d), but they are almost all CD4(-) after positive selection on a class II for which they have higher avidity, IA(b). DO-TCR(+) T cells mature in H-2(b) mice lacking CD4. CD4(-) DO-TCR(+) T cells appear in H-2(b) mice at the same rate as their CD4(+) counterparts appear in H-2(d) animals, suggesting that the CD4(-) cells are not the product of some minor pathway of thymocyte development and selection. In H-2(b) 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.