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. 2008 Aug;57(8):1253-62.
doi: 10.1007/s00262-008-0460-2. Epub 2008 Feb 7.

The neoplastically transformed (CD30hi) Marek's disease lymphoma cell phenotype most closely resembles T-regulatory cells

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The neoplastically transformed (CD30hi) Marek's disease lymphoma cell phenotype most closely resembles T-regulatory cells

L A Shack et al. Cancer Immunol Immunother. 2008 Aug.

Abstract

Introduction: Marek's disease (MD), a herpesvirus-induced lymphoma of chickens is a unique natural model of CD30-overexpressing (CD30hi) lymphoma. We have previously proposed that the CD30hi neoplastically transformed CD4+ T cells in MD lymphomas have a phenotype antagonistic to cell mediated immunity. Here were test the hypothesis that the CD30hi neoplastically transformed MD lymphoma cells have a phenotype more closely resembling T-helper (Th)-2 or regulatory T (T-reg) cells.

Materials and methods: We separated ex vivo-derived CD30hi, from the CD30lo/- (non-transformed), MD lymphoma cells and then quantified the relative amounts of mRNA and proteins for cytokines and other genes that define CD4+ Th-1, Th-2 or T-reg phenotypes.

Results and discussion: Gene Ontology-based modeling of our data shows that the CD30hi MD lymphoma cells having a phenotype more similar to T-reg. Sequences that could be bound by the MD virus putative oncoprotein Meq in each of these genes' promoters suggests that the MD herpesvirus may play a direct role in maintaining this T-reg-like phenotype.

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Figures

Fig. 1
Fig. 1
Difference in cytokine and cell antigen mRNA (a) and protein (c) expression (measured by duplex real-time reverse transcriptase PCR and proteomics as described in M and M) of CD30hi, relative to CD30lo/−, MD lymphoma cells. The amount of CD30lo/− mRNA expression is set to 100% and protein expression is set to 0. The CD30hi, were separated from the CD30lo/−, lymphoma cells by magnetic activated cell sorting. Inset: the mean purity (±SEM) was 95.7 ± 3.3 and 93.9 ± 4.9%, for the (1) CD30hi and (2) CD30lo/− cells, respectively. GO-based hypothesis-driven quantitative modeling as described in M and M for the mRNA (b) and protein (d) shows that the CD30hi cells have a T-reg phenotype
Fig. 2
Fig. 2
Difference in IL-2 and IL-18 protein distribution in CD30lo/− and CD30hi lymphoma cells mean (±SEM). Both IL-2 and IL-18 protein are preferentially distributed in the differential detergent fractions representing the least superficial areas of the cell and the less soluble proteins

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