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 J11d 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 α/β-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.