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Comparison of type 1 and type 2 immune response balance of decidual and blood lymphatic cells during first trimester of pregnancy

Problem: It is believed that an immunity shift from type 1 toward type 2 is essential for the tolerance of the fetus during normal pregnancy. Many studies suggested that increased production of proinflammatory cytokines and dominance of type 1 immunity is accompanied with pathological pregnancies. However, some recent data emphasized the role of the type 1 immunity in maintenance of normal pregnancy. To assess the relevance of both types of immunity in pregnancy we compared the response of different decidual and blood lymphocyte subtypes to in vitro stimulation with type1 or type2 inducible cytokines. Methods of study: Decidual lymphocytes were isolated by ficoll gradient centrifugation of the enzymatically digested decidual tissue obtained from normal first trimester pregnancy and PBLs were isolated from same women by the same method. Cells were cultivated with 20 ng of IL12, IL18 or their combination IL12+IL18, IL15 or IL15+IL18 as well as IL10 or IL10+IL18 during 18 hours, followed by incubation with Brefeldin A for next 5 hours. We determined the effector phenotype of collected cells by intracellular staining of IFN and IL4 and flow cytometry analysis of responding cell subpopulations that were some of the following: CD3+CD4+, CD3+CD8bright, CD3+CD8dim, CD3-CD56bright, CD3-CD56dim, CD3+CD56dim. Results: Both CD3+CD4+ and CD3+CD8+ decidual T cells as well as decidual NKT cells produced IFN after IL12 stimulation while blood CD3+CD8+ T cells were poor IFN producers. Combined IL12+IL18 stimulation induced IFN production in both types of blood T cells and NKT cells, although less than in decidual cells. NK cells showed different pattern of response than T cells. Blood NK cells responded much better to IL12+IL18 stimulation than decidual cells. Conclusion: Taken together data showed that regulated balance of both types of immune response in the first trimester of normal pregnancy is existing and important for the normal pregnancy outcome.

decidual cells; pregnancy; cytokines; NKT cells

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