RESUMO
Recent data suggest a dominant role of the innate, rather than the adaptive immune system in pregnancy-related immunoregulation. gamma/delta T cells, that comprise a minor subpopulation of human peripheral blood lymphocytes, represent a link between the innate and the acquired immune systems. However little is known about how they function in preeclampsia, which is suggested to be associated with a Th1 predominant immune response. The aim of our study was to investigate the presence and phenotype of Vdelta2+ cells and of regulatory T cells in the pathogenesis of preeclampsia. Since Vdelta2+ T cell function has been shown to be altered in patients with preeclampsia we investigated the expression of perforin, Fas and TIM-3 by Vdelta2+ T cells and the possible role of activating and inhibitory NK cell receptors as well as of regulatory T cells. Vdelta2+ T cells of preeclamptic patients demonstrated an increased perforin and IFNgamma production, which could be explained by dysregulation of NK cell receptor expression. These Th1 polarized cells were less susceptible to apoptosis than Vdelta2+ T cells from healthy pregnant women. Our data suggest that activated Vdelta2+ T cells of preeclamptic women have an increased cytotoxic potential, which may be due to altered expression of NK cell inhibitory and activating receptors. In this study we report a series of observations, which taken together suggest the role of multiple pathways in generating an exaggerated systemic inflammatory response observed in the clinical stage of preeclampsia.
Assuntos
Pré-Eclâmpsia/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Apoptose/imunologia , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Imunofenotipagem , Inflamação , Interferon gama/metabolismo , Ativação Linfocitária , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Perforina/genética , Perforina/imunologia , Perforina/metabolismo , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Receptor fas/genética , Receptor fas/imunologia , Receptor fas/metabolismoRESUMO
PROBLEM: Recent data suggest a dominant role of the innate, rather than the adaptive immune system in pregnancy-related immunoregulation. Invariant NKT (iNKT) cells represent a link between the innate and the acquired immune systems; however, little is known about how they function in pre-eclampsia. The aim of our study was to investigate the possible role of iNKT cells in the pathogenesis of pre-eclampsia. METHOD OF STUDY: Human peripheral blood samples were obtained from pre-eclamptic, healthy pregnant- and non-pregnant women. Freshly separated peripheral blood mononuclear cells were immediately labeled with anti-perforin-, anti-CD69-, anti-CD95-, anti-NKG2A-, anti-NKG2D-, anti-IFN-gamma and anti iNKT antibodies and analyzed by flow cytometry. RESULTS: Pre-eclamptic patients demonstrated increased CD69, perforin and IFN-gamma expression, which could be explained by dysregulation of NK cell receptor expression. These Th1 polarized cells were less susceptible to apoptosis than iNKT cells from healthy pregnant women. CONCLUSION: Our data suggest that activated iNKT cells of pre-eclamptic women have an increased cytotoxic potential, which may be because of altered expression of NK cell inhibitory and activating receptors.