engleski

Type 1 versus type 2 immune response balance of decidual innate and adaptive cells during first trimester of pregnancy

Problem: Previous studies have reported the importance of a bias of T cell immunity towards type 2 (Th2) for normal pregnancy outcome. However, some recent studies performed on peripheral blood and decidual lymphocytes showed also relevance of Th1 responses in maintenance of normal pregnancy. To address this problem we studied the expression of IL18Ralpha (which is considered to be a functional marker of type 1 responses) and ST2L (a homologue of IL1R, which is a marker of type 2 responses) on decidual lymphocytes Methods of study: Decidual lymphocytes were isolated by ficoll gradient centrifugation of the enzymatically digested decidual tissue obtained from normal first trimester pregnancy. Expression of IL18Ralpha and ST2L markers were detected on the freshly prepared decidual T-cell subpopulations ; (CD3+CD4+ ; CD3+CD8+), NK cells (CD56brightCD3- ; CD56dimCD3-) and NKT cells (CD56+CD3+) after three-colour immunofluorescence staining with directly and indirectly conjugated antibodies followed by flow cytometry. Results: High expression of IL18Ralpha and low expression of ST2L was detected on all investigated cell populations. Almost 60% of CD3+CD4+ cells express IL18Ralpha, and less than 2% ST2L (Th1/Th2 ratio was 46, 0). Approximately a half of CD3+CD8+ T cells express IL18Ralpha while only less of 2 % ST2L (Tc1/Tc2 ratio was 39, 6). Similar results were obtained on NK cells, but the NK1/NK2 ratio was lower suggesting more of a bias to type 2 than in the T cell populations. Decidual NK cells (CD56+CD3-) and NKT cells (CD56+CD3+) also express predominantly IL18Ralpha (13% and 66, 3% respectively) in comparison to ST2L (1% and 1, 5% respectively). We found stronger IL18R expression on CD56dimCD3- cells than on the CD56brightCD3- (24, 9% and 4, 1%, respectively), but calculated NK1/NK2 ratios for both populations remain very similar, for CD56brightCD3- population ratio was 19, 1 and for CD56dimCD3- population was 17, 2. In contrast, the NKT1/NKT2 ratio was very high (53, 5). Conclusion: High expression of the IL18Ralpha than ST2L on decidual cells of innate and adaptive immunity indicates importance of the type 1 immune response for normal pregnancy maintenance. The experiments are partially financed by Croatian Ministry of Science (Grants No. 0620402-0376 and 0379) and EMBIC project, European FP6, NoE, LSHM-CT-2004-512040.

T cells; Th1; Th2; NKT cells; pregnancy

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