A Viral Long Terminal Repeat Expressed in CD4+CD8+ Precursors Is Downregulated in Mature Peripheral

The long terminal repeat from a thymotropic mouse mammary tumor virus variant, DMBA-LV, was used to drive the expression of two reporter genes, murine c-myc and human CD4, in transgenic mice. Expression was observed specifically in thymic immature cells. Expression of c-myc in these cells induced oligoclonal CD4+CD8+ T-cell thymomas. Expression of human CD4 was restricted to thymic progenitor CD4- CD8- and CD4+CD8+ T cells and was shut off in mature CD4+CD8- and CD4-CD8+ T cells, known to be derived from the progenitor double-positive T cells. These results suggest the existence of similar and common factors in CD4+CD8- and CD4-CD8+ T cells and support a model of differentiation of CD4+CD8+ T cells through common signal(s) involved in turning off the expression of the CD4 or CD8 gene. DMBA-LV leukemia virus is a type B replication-compe-tent thymotropic retrovirus which is highly related to mouse mammary tumor virus (MMTV) (5, 19). However, in con-trast to MMTV, known to induce mammary carcinomas (36), DMBA-LV MMTV (MMTVD) induces a high incidence of T-cell leukemias (thymomas) after a short latent period (6). Sequence analysis of the MMTVD long terminal repea