engleski

Tumor associated glycoprotein-72 (TAG-72) orientates the immune response via CD1a+ dendritic cells

Problem: We evaluate whether Tumor Associated Glycoprotein-72 (TAG-72), which is also physiologically present in decidual glandular cells can affect dendritic cell (DC) functions and orientate cytokine production in T cells. Methods of study: The first trimester human pregnancy decidua was used for immunohistology studies and the isolation of decidual mononuclear cells (DMC) by enzymatic digestion and gradient density centrifugation. The phenotype and cytokine production in decidual CD1a+ DC was assesed by flow cytometry in DMC cultured in the medium only or in the presence of TAG-72 (200 U/mL) for 18 hours. Decidual CD1a+ cells magneticaly separated (purity ~40%) from the adherent DMC fraction were untreated or treated with TAG-72, and co-cultured with CD6 purified cord blood (CB, purity >98%) or decidual T cells (purity ~70%) for 3 or 6 days. Polarization of T cells was measured by analysing interleukin (IL)-4, interferon-gamma (IFN- ) and CD45RA expression. Results: CD1a+ cells are spreaded all over the stroma of decidual tissue and they are found in intimate contact with glandular epithelial cells. TAG-72 decreased maturation markers expression on CD1a+ DC, as well as the production of IL-15 and IFN- . Interleukin-10 was enhanced, wheres IL-18 was unaffected in CD1a+ DC pretreated with TAG-72. Decidual CD1a+ cells enhance IL-4, whereas did not affect IFN- production in CB T cells after 3 and 6 days co-culture at DC/T cell ratio 1:5. TAG-72 treated DC decreased IFN- in CB T cells and sustain IL-4 production in LPS treated CB T cells after 3 days of the co-culture. Concomitant decrease of CD45RA expression on the surface of CB CD3+ cells was noticed. TAG-72 treated CD1a+ cells enhance IL-4 and decreased IFN- in decidual T cells. Conclusions: TAG-72 inhibits the maturation and induce anti-inflammatory properties of decidual CD1a+ DC, that support Th2 orientation of the immune response. Acknowledgement: The experiments are partially financed by the grants of « ; ; EMBIC» ; ; European FP6 project No. 512040, LSHM-CT-2004-512040, as well as Croatian Ministry of Science, Education and Sports, Grants No. 0620402-0376 and No. 0377.

Tumor associated glycoprotein-72; dendritic cells

nije evidentirano