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The Journal of Immunology, 2000, 165: 1236-1242.
Copyright © 2000 by The American Association of Immunologists

Early Onset of CD8 Transgene Expression Inhibits the Transition from DN3 to DP Thymocytes

Andreas Wack1, Mark Coles, Trisha Norton, Arnd Hostert and Dimitris Kioussis2

Division of Molecular Immunology, National Institute for Medical Research, Mill Hill, London, United Kingdom

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 TCRß selection takes place and diminishes expansion at the subsequent developmental stages, resulting in increased DN3 and markedly reduced double-positive (DP) thymocyte numbers. 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 same degree of overexpression on DP thymocytes, but is not expressed on double-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 stages rather than to increased negative selection of DP cells.




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