N-methyl-N-nitrosourea alters thymocyte subset distribution and targets immature CD4-8+ cells for lymphoma development.
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.
Stettner
S L
SL
University of Texas, M. D. Anderson Cancer Center, Smithville 78957.
Rummel
S A
SA
Conti
C J
CJ
Richie
E R
ER
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens; D008223:Lymphoma / Q000139:chemically induced* / Q000276:immunology; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008806:Mice, Inbred AKR; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D013953:Thymus Neoplasms / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D008770:Methylnitrosourea