Early onset of CD8 transgene expression inhibits the transition from DN3 to DP thymocytes

In this paper we show that the effects of transgenic coreceptor expression on thymocyte development depend on the onset of transgene expression. Thus, a CD8 transgene expressed on CD44(+)CD25(+) (DN2) and CD44(-)CD25(+) (DN3) cells causes a partial block at the stage when TCR beta selection takes pl ace and diminishes expansion at the subsequent developmental stages, result ing in increased DN3 and markedly reduced double-positive (DP) thymocyte nu mbers. This effect is evident on a polyclonal TCR repertoire as well as in TCR-transgenic mice (F5), By contrast, a CD8 transgene that leads to the sa me degree of overexpression on DP thymocytes, but is not expressed on doubl e-negative subsets, has no effect on thymus size or composition. Therefore, the reduction of DP thymocyte numbers in CD8 TCRtg mice can be attributed to interferences at early developmental stapes rather than to increased neg ative selection of DP cells.