THE PROGRAMMED CELL-DEATH OF AN IMMATURE THYMOCYTE CELL-LINE TRANSGENIC FOR AN ALPHA-BETA TCR AND THE C-MYC PROTOONCOGENE

The c-myc proto-oncogene linked to the mouse Thy-1 gene transcriptiona l unit predisposes mice to development of thymic tumors consisting pre dominantly of immature CD4(+)CD8(+) cells. In an attempt to immortaliz e immature T cells expressing a known T-cell antigen receptor (TCR), T hy-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-stab le antigen (HSA) and were able to undergo programmed cell death upon i nduction with steroids and CD3 cross-linking, but not with cognate pep tide. In addition, one line had rearranged and transcribed endogenous TCR alpha and beta genes, in spite of the fact that transgenic alpha a nd 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 o rder for thymocytes to be transformed by the Thy-myc transgene, they n eed to proceed to the double-positive stage.