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

• Published in: Molecular immunology Vol. 36; no. 8; pp. 491 - 503
• Main Authors: Morrow, Maureen A, Mayer, Elizabeth W, Perez, Cesar A, Adlam, Matthew, Siu, Gerald
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.1999
• Subjects: AIDS/HIV; Animals; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Division - genetics; Cell Division - immunology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; Female; Helix-Loop-Helix Motifs - genetics; Helix-Loop-Helix Motifs - immunology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Inhibitor of Differentiation Protein 2; Lymphocyte Activation - genetics; Lymphoma, T-Cell - etiology; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Repressor Proteins - genetics; Repressor Proteins - immunology; Spleen - cytology; Spleen - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymus Gland - cytology; Thymus Gland - immunology; Transcription Factors
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/S0161-5890(99)00071-1

The Id proteins are inhibitors of basic–Helix–Loop–Helix transcription factor function that have been implicated in the control of cell differentiation and proliferation. To study the role of Id proteins in the control of T cell development, we generated transgenic mice that overexpress the Id2 protein in thymocytes. We detect a significant expansion of the early CD4 −CD8 +TCR − thymocyte stage and a depletion of the thymocytes of the subsequent developmental stages. These data indicate that the overexpression of Id2 leads to a stage-specific developmental block early in thymopoiesis. In addition, progeny mice from five of the six Id2 transgenic founder lines succumb to aggressive T cell hyperproliferation that resembles lymphoma. Thus, overexpression of the Id2 protein has profound effects on T cell development and oncogenesis, consistent with the hypothesis that the bHLH proteins play critical roles in these processes.