Surface phenotypes in T-cell leukaemia are determined by oncogenic retroviruses

Spontaneous thymic leukaemia in experimental mice is the result of a complex series of genetically controlled events. An important step in this process involves the production by thymocytes of recombinant polytropic retroviruses (MCF viruses). These leukaemogenic agents arise by recombination of genes from the env regions of endogenous precursor viruses. Sequences in these regions encode the envelope glycoprotein gp70 (ref. 6). Thus far, each cloned isolate of recombinant virus from AKR and HRS/J mice has been found to possess unique oligonucleotide sequences in its env region, as well as clone-specific peptides in its gp70 (refs 7,8). Therefore, the polytropic viruses of these leukaemia-susceptible mice are extremely diverse. These findings suggest that random recombination of env genes gives rise to leukaemogenic polytropic viruses. McGrath and Weissman have proposed that thymocytes with cell surface receptors for the gp70 of a particular leukaemogenic virus are the target cells for malignant transformation by that specific virus. In view of the diversity of polytropic viral gp70, their hypothesis would predict extensive phenotypic diversity among spontaneous thymic leukaemias. In contrast, leukaemias induced by a particular leukaemogenic recombinant virus would always have the same phenotype. Here we verify these predictions experimentally.     

A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family

Recent studies have demonstrated that CD3 is expressed on a subset of thymocytes with a CD4-CD8- (double negative) phenotype. At least some of these cells bear the CD3-associated gamma delta T-cell receptor (TCR gamma delta). Here we describe a second subset of double negative thymocytes which expresses CD3-associated alpha beta receptors (TCR alpha beta). Surprisingly, these cells express predominantly the products of a single V beta gene family (V beta 8). These CD4-CD8-, TCR alpha beta+ cells appear relatively late in ontogeny (between birth and day 5 of life) and thus are unlikely to be the precursors to the TCR alpha beta-bearing cells (CD4+CD8- and CD4-CD8+) already present at birth. They can be selectively expanded in vitro by stimulation with a monoclonal antibody to V beta 8 (F23.1) in the presence of interleukin I (IL-1). We propose that this cell type is a unique T-cell population distinguishable from typical TCR alpha beta+ T cells by its CD4-CD8- phenotype and a restricted TCR V beta repertoire. Analysis of the unique phenotype of these cells suggests that they may represent the normal counterpart of the defective CD4-CD8- T cells found in the lpr autoimmune mouse.