Overexpression of the Helix-Loop-Helix protein Id2 blocks T cell development at multiple stages

The Id proteins are inhibitors of basic-Helix-Loop-Helix transcription fact or function that have been implicated in the control of cell differentiatio n and proliferation. To study the role of Id proteins in the control of T c ell development, we generated transgenic mice that overexpress the Id2 prot ein in thymocytes. We detect a significant expansion of the early CD4(-)CD8 (+)TCR(-) thymocyte stage and a depletion of the thymocytes of the subseque nt developmental stages. These data indicate that the overexpression of Id2 leads to a stage-specific developmental block early in thymopoiesis. In ad dition, progeny mice from five of the six Id2 transgenic founder lines succ umb to aggressive T cell hyperproliferation that resembles lymphoma. Thus, overexpression of the Id2 protein has profound effects on T cell developmen t and oncogenesis, consistent with the hypothesis that the bHLH proteins pl ay critical roles in these processes. (C) 1999 Elsevier Science Ltd. All ri ghts reserved.