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 alpha/beta-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.
Richie
E R
ER
University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957.
McEntire
B B
BB
Coghlan
L
L
Poenie
M
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D015704:CD4 Antigens / Q000096:biosynthesis*; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D016399:Lymphoma, T-Cell / Q000139:chemically induced / Q000473:pathology*; D008770:Methylnitrosourea; D051379:Mice; D008806:Mice, Inbred AKR; D009368:Neoplasm Transplantation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000473:pathology
D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D008770:Methylnitrosourea