Thymocyte expressing CD8 differentiate into CD4⁺ cells following intrathymic injection

Based on the cell surface expression of CD4 and CD8 molecules, murine thymocytes can be divided into four populations: these include CD4^-, CD8^- double-negative and CD4⁺, CD8⁺ double-positive subpopulations, both of which consist largely of immature cells, and the single positive, CD4⁺ or CD8⁺, subsets that contain functional helper or killer cells, respectively. The double-negative subset contains precursors of the other three populations and can reconstitute the thymus following intravenous or intrathymic transfer into irradiated hosts. In an attempt to establish the sequence of CD4 and CD8 expression during intrathymic development, we investigated the differentiation potential of highly purified CD8⁺ thymocytes by using intravenous or intrathymic adoptive transfer. Unlike the double-negative thymocyte subset, CD8⁺ cells did not have the ability to home to the thymus following intravenous transfer. However, when CD8⁺ thymocytes were injected directly into the thymus, they increased in number and gave rise to CD4⁺, CD8⁺ double-positive and CD4⁺ single-positive progeny. Furthermore, the rate of appearance of CD4⁺ cells from injected CD8⁺ precursors was faster than from the double-negative subset. Cells expressing a high surface density of CD8 convert to double-positive and CD4⁺ progeny without increasing in number, whereas CD8⁺ cells expressing a low surface density of the marker expand greatly and give rise to differentiated progeny. The results suggest that CD8 expression is an intermediate step on the differentiation pathway of mature CD4⁺ T cells.