The programmed cell death of an immature thymocyte cell line transgenic for an alpha beta TCR and the c-myc proto-oncogene.
The c-myc proto-oncogene linked to the mouse Thy-1 gene transcriptional unit predisposes mice to development of thymic tumors consisting predominantly of immature CD4+ CD8+ cells. In an attempt to immortalize immature T cells expressing a known T-cell antigen receptor (TCR), Thy-1/c-myc transgenic mice were bred to alpha beta TCR transgenic mice (F5), and CD4+ CD8+ cell lines were established from thymic tumors in double-transgenic mice. These cells expressed high-level heat-stable antigen (HSA) and were able to undergo programmed cell death upon induction with steroids and CD3 cross-linking, but not with cognate peptide. In addition, one line had rearranged and transcribed endogenous TCR alpha and beta genes, in spite of the fact that transgenic alpha and beta genes were also expressed. Furthermore, we show that Thy-1/myc transgenic mice deficient in recombination activating gene-1 (RAG-1) do not develop tumors, in contrast to RAG-1-/- mice, which are also transgenic for both Thy-1/myc and the F5 TCR. This indicates that in order for thymocytes to be transformed by the Thy-myc transgene, they need to proceed to the double-positive stage.
Murdjeva
M
M
Laboratory of Molecular Immunology, National Institute for Medical Research, London, UK.
Tanaka
Y
Y
Norton
T
T
Kioussis
D
D
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002461:Cell Line, Transformed; D015329:Gene Rearrangement, T-Lymphocyte; D016654:Genes, RAG-1; D016259:Genes, myc; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens / Q000235:genetics; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018800:Thy-1 Antigens