Two differential pathways from double-negative to double-positive thymocytes

Murine thymocytes are divided into four major populations on the basis of expression of CD4 and CD8 antigens. The bulk of evidence favours the view that CD4^-CD8^- cells can develop into CD4^-CD8⁺ and CD4⁺CD8^- cells via the CD4⁺CD8⁺ stage in the thymus. However, CD4^-CD8⁺ and CD4⁺CD8^- thymocyte subsets contain not only CD3⁺ mature cells but also CD3^- immature cells, which seem to be intermediate cells between CD4^-CD8^- and CD4⁺CD8⁺ cells. Here we demonstrate mouse stain differences in the proportion of immature single-positive thymocyte subsets in thymus at the steady or developing state. In C3H mice, immature CD4⁺CD8^- is dominant in proportion over CD4^-CD8⁺ in foetal thymus and in donor-derived thymocytes at an early stage of bone marrow transplantation. On the other hand, immature CD4^-CD8⁺ is dominant over CD4⁺CD8^- during T-cell development in the case of B10.BR mice. An intermediate pattern was shown in the case of F₁ mice. Both of these immature single-positive subsets gave rise to double-positive cells after 24 hr culture. These results suggest that there exist two distinct differential pathways; one is from CD4^-CD8^- cells to CD4⁺CD8⁺ cells via CD4^-CD8⁺ cells, and another is via CD4⁺CD8^- cells, and that an application of the 'CD8 pathway' or 'CD4 pathway' seems to be genetically destined by BM-derived cells but not by thymic stromal cells.