Murine T-Lymphomas Corresponding to the Immature CD4"8+ Thymocyte Subset

N-methyl-N-nitrosourea induces murine CD4“8+ T-lymphomas that express high levels of Jlld and low levels of CD5 antigens, a phenotype characteristic of immature CD4~8+ thymocytes. This assignment is supported by the fact that CD4~8+ lymphoma cell lines acquire CD4 expression after intrathymic (i.t.) transfer, a finding consistent with the established precursor potential of the normal immature CD4~8+ subset. CD4+8+ lymphomas recovered after i.t. transfer maintain a CD4+8+ phenotype in long-term culture. Northern blot analyses reveal that CD4 expression is regulated at the transcriptional level in immature CD4"8+ and CD4+8+ cell lines. CD4~8+ lymphomas express low levels of functional CD3/TCR complexes that mediate intracellular Ca2+ mobilization in response to CD3 or a/ß-TCR monoclonal antibody. These data suggest that the immature CD4~8+ subset contains cells capable of undergoing TCR-mediated signaling and selection events. In contrast to normal immature CD4"8+ cells, which comprise a heterogeneous and transient subset, the CD4"8+ lymphoma lines provide stable, monoclonal models of the immature CD4"8+ stage of thymocyte development.