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N-methyl-N-nitrosourea alters thymocyte subset distribution and targets immature CD4-8+ cells for lymphoma
S L Stettner1, S A Rummel, C J Conti
1University of Texas, M. D. Anderson Cancer Center, Smithville 78957.
The majority of N-methyl-N-nitrosourea (MNU)-induced lymphomas in AKR/J mice express a CD4-8+ phenotype. The CD4-8+ subset in normal thymus contains functionally mature medullary cells and immature cycling cells. This study demonstrates that MNU-induced lymphomas correspond to the immature CD4-8+ subset. In addition, specific changes in the distribution of thymocyte subsets defined by CD4 and CD8 expression were observed after MNU treatment. Cortical thinning and selective depletion of immature CD4-8+ and CD4+8+ subsets occur immediately after treatment. In contrast, immature CD4-8- progenitors and mature medullary CD4+8- and CD4-8+ subsets are relatively resistant to cytotoxicity. Normal thymic architecture and subset distribution are restored within 2 weeks after which selective expansion of the immature CD4-8+ subset occurs. The data suggest that MNU induces neoplastic conversion in progenitor cells corresponding to the CD4-8- or immature CD4-8+ stages of thymocyte maturation.
The majority of N-methyl-N-nitrosourea (MNU)-induced lymphomas in AKR/J mice express a CD4-8+ phenotype. The CD4-8+ subset in normal thymus contains functionally mature medullary cells and immature cycling cells. This study demonstrates that MNU-induced lymphomas correspond to the immature CD4-8+ subset. In addition, specific changes in the distribution of thymocyte subsets defined by CD4 and CD8 expression were observed after MNU treatment. Cortical thinning and selective depletion of immature CD4-8+ and CD4+8+ subsets occur immediately after treatment. In contrast, immature CD4-8- progenitors and mature medullary CD4+8- and CD4-8+ subsets are relatively resistant to cytotoxicity. Normal thymic architecture and subset distribution are restored within 2 weeks after which selective expansion of the immature CD4-8+ subset occurs. The data suggest that MNU induces neoplastic conversion in progenitor cells corresponding to the CD4-8- or immature CD4-8+ stages of thymocyte maturation.