Expression of CD28 and cytotoxic T lymphocyte antigen 4 at the maternal-fetal interface in women with unexplained pregnancy loss

Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
International Journal of Gynecology & Obstetrics (Impact Factor: 1.56). 05/2006; 93(2):123-9. DOI: 10.1016/j.ijgo.2006.01.027
Source: PubMed

ABSTRACT To investigate the expression of CD28 and CTLA-4, two costimulatory molecules involved in T-cell activation at the maternal-fetal interface in women with unexplained pregnancy loss.
A total of 57 women, 39 with unexplained spontaneous abortion (SA) and 18 with unexplained recurrent spontaneous abortion (RSA), were enrolled in the study. A high-resolution spectratyping analysis of fluorescent bands was performed to detect CD28 and CTLA-4 expression in decidual tissues.
The mean expression of CTLA-4 mRNA was significantly higher in women with SA than in controls (P<0.05). Moreover, the expression of CTLA-4 was higher in SA patients with genotype AA and phenotype A+ (AA+AG) than in controls (P<0.01). The expression of CTLA-4 was not significantly different in patients with RSA and in controls. The expression of CD28 was significantly decreased in patients with RSA (P<0.01) and SA (P<0.05) compared with controls. The mean ratios of CTLA-4/CD28 were significantly higher in patients with RSA (P<0.01) and SA (P<0.05) than in controls.
This study suggests that an imbalance in CTLA-4/CD28 expression or suppressed T-cell activity at the maternal-fetal interface may confer susceptibility to unexplained pregnancy loss.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The costimulatory molecules CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) (cytotoxic T-lymphocyte-associated antigen-4) and inducible costimulator (ICOS) are believed to have a critical modulatory role in the immune response. However, few studies have been performed on the role of these immune regulatory molecules and their polymorphisms in women with preeclampsia (PE). The aim of our study was to evaluate the CTLA4 (+49 A/G) (rs 231775), CD28 (+17 T/C) (rs 3116496) and ICOS (-1564 T/C) (rs 4675378) gene polymorphisms in Brazilian women with PE. This case-control study included 130 patients with PE and 261 control women without any obstetric or systemic disorders. Genomic DNA was extracted from peripheral blood, and the polymorphism genotyping was performed by digesting the PCR products with the restriction endonucleases BbvI (CTLA-4), AfeI (CD28) and AluI (ICOS). Data were analyzed by χ(2) or Fisher's exact test; a P-value of <0.05 was considered as significant. There were significant differences in the ICOS genotype and allelic frequencies between the PE and control groups (P=0.01 and P=0.01, respectively). We found a significantly lower frequency of the ICOS (-1564) T allele in women with mild PE compared with the controls. There were no differences in the CTLA-4 (+49 A/G) and CD28 (+17 T/C) genotypes and allelic frequencies between the PE patients and controls. Our data suggest that PE is associated with ICOS, but is not associated with the CTLA-4 or CD28 gene polymorphisms.
    Hypertension Research 12/2010; 34(3):384-8. DOI:10.1038/hr.2010.247 · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A pregnancy is associated with modifications in the immune status of the mother, but the mechanisms are not well understood. Several observations have indicated that CD28/CTLA-4 and B7-1/B7-2 are involved in the maternal-fetal immune regulation. This review aims to recapitulate our current knowledge concerning the role of CD28/CTLA-4 and B7-1/B7-2 in maternal-fetal immune regulation. Several studies suggest that up-regulation of B7-2 and/or CD28 and/or down-regulation of CTLA-4 are correlated with the occurrence of pregnancy loss. Therefore, an accurate expression of costimulatory molecules at the maternal-fetal interface may ensure that the decidual cells do not elicit a 'danger' signal to the maternal immune system, perhaps instead contributing to the establishment of immune tolerance in vivo. It is showed that costimulation blockade with anti-B7 mAbs results in altered allogeneic T-cell response and overcomes increased maternal rejection to the fetus, which improves fetus growth in the abortion-prone system. These findings suggest that the anti-B7-treated T cells not only function as potent suppresser cells but also exert immunoregulatory effect on the maternal T cells. This procedure might be potentially useful to immunotherapy for human recurrent spontaneous abortion.
    American Journal Of Reproductive Immunology 08/2011; 66(2):76-83. DOI:10.1111/j.1600-0897.2010.00982.x · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The CD28 and CTLA-4 are important co-stimulatory molecules expressed on T cells and regulate T cell activation through antigen stimulation. This study aimed to investigate some properties of these genes and its products; such as the homologous protein sequences to human CTLA-4 and CD28 molecules, the common transcription factor binding sites on their promoters, and phylogenetic relationships of their Immunoglobulin V-Type (IGv) domains using bioinformatical approaches. Our results revealed that both CTLA-4 and CD28 molecules are moderately conserved among all organisms investigated. The IGv domains of human CTLA-4 and CD28 are closest to those of Macaca nemestrina, Cercocebus torquatus atys , Macaca mulatta and Papio cynocephalus anubis . In contrast, the IGv domain of CD28 of Gallus gallus and that of CTLA-4 of Mus musculus and Rattus norvegicus is most apart from those of human, respectively. The comparative screening of the promoters revealed that both CTLA-4 and CD28 genes have some conserved transcription factor binding sites.