The influence of rearranged T cell receptor αβ transgenes on early thymocyte development

Most murine thymocytes and mature T cells originate from a numerically minor population of CD8⁻4⁻ (double‐negative, DN) thymocytes. In this study, we investigated the effects of rearranged T cell receptor (TcR) α and β transgenes on early T cell development. We analyzed the precursor potential, the expression of CD25 and TcR at mRNA and/or protein level in DN thymocyte subsets in TcR transgenic (Tg) mice. We report the following observations: (i) despite a large overrepresentation of total DN cells in TcR Tg mice, precursor‐containing CD25⁺ DN and CD8¹⁰4¹⁰ thymocytes are reduced to a third of the nontransgenic control numbers; (ii) like in the normal mice, CD25⁺ DN and CD8¹⁰4¹⁰ can, and TcR⁺ DN cells cannot generate other thymic subsets; (iii) TcR α mRNA and TcR α/β protein levels are quantitatively increased, but their developmental expression is similar to that in normal mice; and (iv) surface TcR αβ expression becomes detectable as the thymocytes down‐regulate CD25, paralleling the situation in normal mice. Our findings implicate stringent transcriptional control, rather than TcR gene rearrangement, as a decisive regulator of TcR αβ expression in early ontogeny.