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

Abstract

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. 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. 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.