%0 Journal Article
%T ret/PTC-1 expression alters the immunoprofile of thyroid follicular cells
%A Karen Denning
%A Paul Smyth
%A Susanne Cahill
%A Jinghuan Li
%A Richard Flavin
%A Sinead Aherne
%A John J O' Leary
%A Orla Sheils
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-44
%X A 2 ¡Á 2 matrix comprising Nthy-ori and TPC-1 cell lines and H.T. and control lymphocyte supernatant was designed and utilised as follows; activated lymphocytic supernatant from a H.T. and normal control were co-cultured with a cell line derived from normal thyroid (Nthy-ori) and also a cell line derived from a papillary thyroid carcinoma that endogenously expresses ret/PTC-1 (TPC-1). The co-cultures were harvested at 0, 6 and 18 hour time points. Gene expression analysis was performed on RNA extracted from thyrocytes using TaqMan£¿ Immune profiling Low-Density Arrays (Applied Biosystems, CA, USA) comprising gene expression markers for 93 immune related targets plus 3 endogenous controls.Stimulation of the normal thyroid cell line model with activated T cell supernatant from the H.T. donor yielded global up-regulation of immune targets when compared with control supernatant stimulation. In particular, a cohort of targets (granzyme B, CD3, CD25, CD152, CD45) associated with cytotoxic cell death; T cell receptor (TCR) and T cell signaling were up-regulated in the normal cell line model. When the ret/PTC-1 expressing thyroid cell line was co-cultured with H.T. lymphocyte supernatant, in comparison to control supernatant stimulation, down-regulation of the same subset of immune targets was seen.Co-culturing H.T. lymphocyte supernatant with a normal thyroid cell line model leads to over-expression of a subset of targets which could contribute to the pathogenesis of H.T. via cytotoxic cell death and TCR signalling. Stimulation of the ret/PTC-1 positive cell line with the same stimulus led to a down-regulated shift in the gene expression pattern of the cohort of immune targets. We hypothesize that ret/PTC-1 activation may dampen immunogenic responses in the thyroid, which could possibly facilitate papillary thyroid carcinoma development.Lymphocytic infiltration is a feature of many thyroid diseases, both benign and malignant. Hashimoto Thyroiditis (H.T.), an autoimmune thyro
%U http://www.molecular-cancer.com/content/7/1/44