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

Abstract

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.

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