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Problem: The prevalence of regulatory T cells (Tregs) is lower in preeclampsia (PE) compared to healthy pregnancy (HP). However, the proportion of recently described Treg subtypes has not been investigated. Method: Peripheral blood samples of 19 PE and 21 HP women in the third trimester were evaluated using flow cytometry for the prevalence of activated T cells and naive, effector, thymic, extrathymic, and exhausted Tregs. Results: The prevalence of activated T cells and exhausted Tregs was higher in PE than in HP. The prevalence of the functionally most active effector Tregs is decreased, while naive Tregs appear to be unaffected in PE compared to HP. No difference was detected between Tregs according to their origin (thymic or extrathymic). Conclusion: The combination of lower effector Treg and higher exhausted Treg prevalence may account for the decrease in the functionality of Tregs in PE.

Problem We determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B-7H2, and that of T cells and T helper cells expressing CD28, CTLA-4, PD-1, and ICOS in peripheral blood samples from normal pregnant (NP) and pre-eclamptic (PE) women. We also examined the intracellular expression of indoleamine-2,3-dioxygenase (IDO). Method of study We measured the expression of the above markers using flow-cytometry in peripheral blood samples from 20 NP and 20 PE women in the third trimester. Results The frequency of B7-1 and B7-2 expressing activated monocytes and that of IDO expressing T-lymphocytes was lower in PE than in NP. Conclusion Lower expression of B7-1 and B7-2 proteins on peripheral monocytes in PE might indicate a secondary regulatory mechanism in response to the ongoing systemic maternal inflammation. IDO plays an important role in the pregnancy-specific immune tolerance, and might be a contributing factor in the pathogenesis of PE.

Problem Regulatory T cells (Tregs) play an important role in the development of pregnancy-specific immune tolerance. We aimed to determine the peripheral frequency of a recently described Treg subpopulation, the CD4+ CD25− FoxP3+ Treg subset, and its correlation with the conventional CD4+ CD25high FoxP3+ Tregs in normal pregnancy (NP) and pre-eclampsia (PE) compared to non-pregnant (non-P) women. We also examined the proportion of the activated CD4+ CD25high FoxP3high Treg subset within conventional Treg cells. Method We took peripheral blood samples from 20 PE, 20 NP, and 12 non-P women and determined the frequency of the above Treg subsets using flow cytometry. Results The frequency of conventional CD4+ CD25high FoxP3+ Tregs and activated CD4+ CD25high FoxP3high Tregs, but also that of non-conventional CD4+ CD25− FoxP3+ Tregs was higher in NP compared to non-P women, but lower again in PE, reaching comparable levels to the non-P group. The ratios of CD4+ CD25high FoxP3+ and CD4+ CD25− FoxP3+ Treg subsets were constant in all three investigated groups. Conclusion Our results indicate that the frequency of conventional and non-conventional Tregs alters simultaneously, and the presence in circulation of both of these Treg subsets is similarly important in the adequate development of pregnancy-specific immune tolerance.

Citation Toldi G, Rigo J Jr, Stenczer B, Vasarhelyi B, Molvarec A. Increased prevalence of IL-17-producing peripheral blood lymphocytes in pre-eclampsia. Am J Reprod Immunol 2011; 66: 223–229 Problem Systemic inflammation is a dominant component in the pathogenesis of pre-eclampsia. Besides the imbalance of Th1 and Th2 cells, alterations of the prevalence of Th17 and regulatory T cells have also been suggested to contribute to inflammation. We aimed to describe the prevalence of these four CD4 lymphocyte subtypes in pre-eclampsia and normal pregnancy, along with that of IL-17-producing CD8 and NK cells. Method of study Twenty pre-eclamptic and 22 normal pregnant women were enrolled in this study. Using flow cytometry, we determined the prevalence of IL-17-producing cells among the CD4, CD8 and NK cell subsets. Furthermore, we measured the prevalence of CD4+ Tregs, and Th1/Th2 cells were characterized using cell surface chemokine receptor markers. Results We demonstrated that there is a shift not only in the Th1/Th2 but also in the Th17/Treg balance favouring skewness towards a pro-inflammatory status in pre-eclampsia. The proportion of CD8 and NK cells that express IL-17 was also higher in pre-eclampsia. Conclusion The prevalence of IL-17-producing CD4, CD8 and NK cells is elevated in pre-eclampsia, indicating that both the innate and adaptive arms of the immune system are involved in the development of the exaggerated maternal systemic inflammation observed in this pregnancy-specific disorder.

Citation Bohacs A, Cseh A, Stenczer B, Muller V, Galffy G, Molvarec A, Rigo J Jr, Losonczy G, Vasarhelyi B, Tamasi L. Effector and regulatory lymphocytes in asthmatic pregnant women. Am J Reprod Immunol 2010; 64: 393–401 Problem Asthma influences pregnancy outcome and pregnancy affects asthma severity, but the immunologic mechanisms of these interactions are not fully elucidated. Method The prevalence of lymphocyte subsets was identified by cell surface markers and intracellular FoxP3 staining, in healthy non-pregnant (HNP; N = 15), healthy pregnant (HP; N = 33), asthmatic non-pregnant (ANP; N = 62) and asthmatic pregnant (AP; N = 61) women. Results Regulatory T cell (Treg) prevalence was higher in HP than in HNP subjects and showed a positive correlation with fetal birth weight, which was blunted in AP group. Treg prevalence was lower and invariable natural killer T cell prevalence was higher in AP patients (compared to HP). Higher naive and lower effector T cell prevalence was observed in AP than in ANP group. Conclusion Pregnancy-induced increase in Treg cell prevalence is absent in asthmatic pregnancy that may interfere with physiological intrauterine growth. However, pregnancy-specific inhibition of asthmatic inflammation can be detected in uncomplicated asthmatic pregnancy.