3a). However, L61 is also pro Th-1 and anti Th-2, whereas L72 is anti Th-1 and pro Th-2. At the level of JQ1 manufacturer developing microscopic MD-lesions (tumor microenvironment), both L61 and L72 are similarly high pro T-reg and in contrast to the

whole tissues, both L61 and L72 are anti-Th-1, pro Th-2 and anti-inflammatory (Fig. 3b). Fig. 3 Gene ontology (GO)-based quantitative modeling shows that at the whole tissue level both the resistant L61and the susceptible L72 genotype have a pro T-reg microenvironment but also L61 has a pro Th-1 and anti Th-2 microenvironment while susceptible genotypes have the opposite (a). Microscopic lesions in both L61 and L72 have a common phenotype which is pro T-reg, pro Th-2 and anti Th-1 which is antagonistic to cytotoxic T cell mediated immunity (b) Discussion Here we have identified the micro-environments of MD tumors at both the whole tissue and microscopic lesion level at the seminal time-point of lymphoma regression and progression in a natural animal model of CD30-overexpressing lymphoma. We used mRNA expression data from a panel of defining genes, to perform GO based quantitative hypothesis testing to GSK2245840 order validate

our hypothesis that the tissue micro-environment is compatible with the genotype in which lymphoma regression occurs and not in the genotype with lymphoma progression. In the MD system the role of cytokines has previously been focused on Linsitinib molecular weight the virological (rather than neoplastic transformational) stages [20, 23–28]. Xing and Schat [25] proposed that IFNγ and nitric oxide (NO) may affect MDV pathogenesis. Kaiser et al. [20], like us, leveraged the power of MD-resistant and -susceptible chicken genotypes to compare cytokine expression in splenocytes and proposed that IL-6 and IL-18 may play an important role in immune the response that could lead to lymphoma progression in susceptible genotypes and what they Dichloromethane dehalogenase referred to as the maintenance of latency in resistant genotypes. More recently,

Heidari et al. [28] suggested a Th-2 cytokine profile (upregulated IL-4, IL-10, IL-13) in chicken splenocytes in the cytolytic phase of MD. Though splenocytes are one model for studying the immunity and MDV pathogenesis, they may not mimic the MD tissue and tumor microenvironment in non-lymphoid tissues. Regardless, none of the preceding work took the descriptive quantitative genetics to functional modeling. The increase in IL-18 mRNA in L61 that we measured contrasts with Kaiser’s data [20] in which there was no increase in IL-18 mRNA in resistant genotypes when compared to age matched uninfected controls. We did not detect IL-2 mRNA in either whole tissue or microscopic lesions in both L61 and L72. IL-2 is a crucial immune-modulator cytokine for T cell proliferation and is required for maintenance of T-reg cells in vivo [29].