Caratterizzazione fenotipica e funzionale delle cellule dendritiche di sangue periferico : uno strumento nel monitoraggio della gravidanza fisiologica e patologica

DCs are widely distributed potent antigen presenting cells (APC) which play a pivotal role in the orchestration of innate and adaptive immune response. Peripheral blood DCs (pbDCs) are the most accessible source of DCs and the evaluation of their response after encounter of specific stimuli could help in the comprehension of immunological mechanism of many pathologies. DCs circulate in peripheral blood as myeloid (mDCs) and plasmacytoid DCs (pDCs) that differ each other in origin, surface markers and function. Pregnancy represents a major challenge to the maternal immune system, which must tolerate fetal alloantigens encoded by paternal genes to allow survival and growth of the fetus. The DCs involvement during pregnancy is still under intense debate. DCs during pregnancy have been mainly characterized at the maternal-decidual interface where play an important role in maintenance of feto-maternal tolerance, while pbDCs have been poorly investigated so far. On this purpose we developed a six-color flow cytometric method dedicated to the analysis of pbDCs characterization and response on whole blood samples during healthy and pathological human pregnancy progression. We demonstrated that during late pregnancy, mDCs and pDCs are both induced to a state of incomplete activation characterized by increased expression of costimulatory molecules and production of cytokines, but lacking HLA-DR up-regulation. The use of a multiparametric approach, to the study of DCs, allowed us to further demonstrate that the lower expression of HLA-DR molecules on mDCs and pDCs during late healthy pregnancy is restricted to activated DCs, suggesting that the constitutive expression of HLA-DR molecules is unaffected, while its up-regulation is partially inhibited during mDCs and pDCs activation. PBMCs cultures from nonpregnant controls incubated with plasma from pregnant women could demonstrate the contribution of soluble plasmatic factors to the incomplete DCs activation. We also applied the six-color flow cytometric method to characterized pbDCs in one of the most frequent pathological pregnancy: intrauterine growth restriction (IUGR). Unexpectly mDCs and pDCs showed a state of less activation and produced fewer amounts of cytokines than age matched physiological pregnancy. We suggest that a possible inadequate immunological HLA interaction could occour between feto-maternal immune system. This idea is support by recent finding that HLA mismatch could be involved in IUGR etiopathogenesis.