engleski

Tumor associated glycoprotein-72 inhibits the maturation and induces anti-inflammatory properties of decidual CD1a+ dendritic cells

Problem: The aim of this study was to evaluate the effect of physiologically present glandular mucin, tumor associated glycoprotein-72 (TAG-72), on the phenotype and function of decidual CD1a+ dendritic cells (DC). Methods of study: Distribution of CD1a+ cells was analyzed by imunohistology in normal human first trimester pregnancy decidua. Decidual mononuclear cells (DMC) were obtained by enzymatic digestion and gradient density centrifugation. The phenotype and cytokine production in decidual CD1a+ DC was analysed by flow cytometry in DMC cultured in the presence of TAG-72 (200U/mL) or in the medium only for 18 hours. Decidual CD1a+ cells magnetically separated (purity ~40%) from the adherent DMC fraction were untreated or TAG-72 treated, and co-cultured with CD6 purified cord blood or decidual T cells for 3 or 6 days. Polarization of T cells was measured by analysing IL-4, IFN- and CD45RA expression. Results: Decidual CD1a+ cells within decidua are found in a close contact with glandular cells. TAG-72 decreased the expression of maturation markers (CD83, CD80, CD86 and HLA-DR) on CD1a+ DC. The production of IL-15 and IFN- was decreased, IL-10 was enhanced, wheres IL-18 was unaffected in CD1a+ DC pretreated with TAG-72. TAG-72 pretreated CD1a+ DC increased IL-4 and abolished IFN- production in cord blood and decidual T cells after 3 and/or 6 days of culture at the DC/T cell ratio 1:5. Concomitant decrease of CD45RA expression on the surface of CD3+ cells was noticed. Conclusions: TAG-72 inhibits the maturation and induce anti-inflammatory properties of decidual CD1a+ DC. The experiments are partially financed by Croatian Ministry of Science (Grants No. 0620402-0376 and 0377) and EMBIC project, European FP6, NoE, No. 512040, LSHM-CT-2004-512040.

dendritic cells; pregnancy; tumor associated glycoprotein-72 (TAG-72)

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