RESUMO
OBJECTIVES: To investigate the frequency and function of CD4(+)CD25(+)CD127(dim/-) regulatory T (Treg) cells in decidua of patients with unexplained recurrent spontaneous miscarriage (URSM). STUDY DESIGN: The decidual lymphocytes from patients who experienced URSM and normal pregnant women (controls) were collected by Ficoll density gradient centrifugation. CD4(+)CD25(+)CD127(dim/-) Treg cells were isolated by magnetic cell sorting. The proportion of Treg cells and IL-10, TGF-ß in Treg cells were determined by flow cytometry. Inhibitory effects of Treg cells on effecter T cells were detected with or without the presentation of anti-IL-10 antibodies and anti-TGF-ß antibodies. RESULTS: The frequency of CD4(+)CD25(+)CD127(dim/-) Treg cells was decreased in URSM decidua compared to controls (2.09%±0.86% vs. 2.97%±1.19%, p=0.005), and the expression of IL-10 and TGF-ß in Treg cells was lower in the URSM group than in the control group (p=0.04 and p=0.01, respectively). Furthermore, the suppressive effect of CD4(+)CD25(+)CD127(dim/-) Treg cells on the proliferation of effector T cells was decreased in URSM decidua (p<0.05). Suppression was mediated predominantly through IL-10 and TGF-ß in decidua. CONCLUSIONS: Decreased frequency and immunosuppressive capacity of CD4(+)CD25(+)CD127(dim/-) Treg cells was found in URSM decidua. Treg cells inhibit proliferation of effector T cells mainly via IL-10 and TGF-ß in URSM decidua.
Assuntos
Aborto Habitual/imunologia , Decídua/patologia , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Aborto Habitual/metabolismo , Aborto Habitual/patologia , Adulto , Proliferação de Células , Separação Celular/métodos , Células Cultivadas , Decídua/imunologia , Feminino , Citometria de Fluxo , Humanos , Tolerância Imunológica , Interleucina-10/antagonistas & inibidores , Interleucina-10/metabolismo , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismoRESUMO
T helper 17 (Th17) cells and regulatory T (Treg) cells are two distinct subsets of CD4(+) T cells which have opposite effects on inflammation, autoimmunity and immunological rejection of foreign tissue. Treg cells have been shown to be important in maintaining materno-fetal tolerance, but the role of Th17 cells in human pregnancy and pathological pregnancy, especially in relation to unexplained recurrent spontaneous abortion (RSA), has not been investigated. In this study, we showed that the proportion of Th17 cells in the peripheral blood and decidua was significantly higher in unexplained RSA patients compared to normal, early pregnant women. Meanwhile, there was an inverse relationship between Th17 cells and Treg cells in the peripheral blood lymphocytes (PBL) and decidua in unexplained RSA. The expression of Th17 related factors, IL-17, IL-23 and retinoid orphan nuclear receptor (RORC), in PBL and decidua in unexplained RSA patients was significantly higher than normal, early pregnant women. This study is the first to define the occurrence of Th17 cells in unexplained RSA patients and in normal, early pregnant women. We suggest that these highly pro-inflammatory cells contribute to unexplained RSA, and the balance between Th17 cells and Treg cells may be critical to pregnancy outcomes.
