ASRI2005-88 Comparable levels of CD4+CD25+ CTLA4+ Treg cells in peripheral blood of pre-eclampsia and normal pregnant patients

June 8, 2017 | Autor: Maria Zenclussen | Categoría: Immunology, Clinical Sciences, Pre Eclampsia
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AJRI American Journal of Reproductive Immunology

ABSTRACTS FROM THE 25TH ANNIVERSARY MEETING OF THE AMERICAN SOCIETY OF REPRODUCTIVE IMMUNOLOGY, PROVIDENCE, RHODE ISLAND, USA JUNE 16–18, 2005

These are the additional abstracts from the 25th Anniversary ASRI meeting in Providence, Rhode Island. These abstracts were inadvertently left out of the abstract issue published in June 2005

ABSTRACTS

ASRI2005-86

Ovine Mx1 associates with microtubules during metaphase and with intercellular bridges between dividing cells K Toyokawa, KG Carnahan, TL Ott Department of Animal and Veterinary Science, Center for Reproductive Biology, University of Idaho, Moscow, USA

Mx proteins are 70–80 kD intracellular antiviral proteins induced by viruses and type I interferons (IFNs). Mx proteins belong to the dynamin superfamily of large GTPases, thought to regulate endocytosis, intracellular vesicle trafficking and cytokinesis. Although antiviral Mx proteins are highly inducible during early pregnancy by embryo-derived IFN tau, cellular functions of Mx proteins in uninduced cells are poorly defined. To better understand the physiological role of Mx proteins during early pregnancy, expression and localization of ovine Mx1 (oMx1) protein were determined in a uterine derived cell line (oGE). oMx1 and beta tubulin were immunolabeled in cells at different stages of the cell cycle. oMx1 was uniformly distributed in the cytoplasm during interphase in the absence of roIFN tau, whereas oMx1 aggregated around vacuoles near the surface of the cells in the presence of roIFN. Interestingly, oMx1 co-localized with mitotic spindles during metaphase. During telophase, oMx1 co-localized with remnants of mitotic spindles at intercellular bridges between dividing cells. Our findings are consistent with a role for Mx1 in secretion by oGE cells and indicate that oMx1 may be involved in cell division. Supported in part by USDA NRICGP grant 2002-02398 and NIH NCRR grant P20RR15587-01 to T.L.O.

ASRI2005-87

Generation of treg cells in the CBA/J · DBA/2J combination by vaccination with male BALB/c splenocytes rescues from abortion A Sollwedel, A Zambon Bertoja, ML Zenclussen, S Ritschel, I Wollenberg, K Gerlof, HD Volk, AC Zenclussen Reproductive Immunology Group, Institute of Medical Immunology, BMFZ, Charite´, Berlin, Germany

We recently described the important role of T-regulatory cells (T-reg) in avoiding fetal rejection in a 120

murine model. In our study, the transfer of Treg obtained from BALB/c-mated CBA/J females into DBA/2J-mated CBA/J completely prevented immunological rejection of the fetuses. Further, a previous study from Chaouat et al. (1993) described that previous vaccination with male BALB/c lymphocytes also prevents abortion. Here, we aimed to analyze if the transfer of male BALB/c lymphocytes was able to expand the Treg population in abortion-prone mice, which would explain the low abortion rates. CBA/J females were treated intraperitoneally (i.p.) with either PBS or 1 · 107 splenocytes from male BALB/c from male BALB/c. 2 days later, the mice were paired with DBA/2J males. On On the 14th day of pregnancy, the mice were sacrificed, the abortion rate was calculated and the ex-vivo Th1/Th2 production was analyzed by flow cytometry. Further, Treg were isolated from spleen and thymus and further transferred into 0–2 days pregnant CBA/J females. As already reported, the BALB/c cell treatment was effective in preventing abortion. This treatment expanded the peripheral spleen Treg population. Treg isolated from mice rescued from abortion were able to prevent abortion in DBA/2J-mated CBA/J females. Our results suggest that the reduced abortion rate observed, after transfer of lymphocytes from BALB/c male is due expansion of the Treg population. Our data suggest that Treg act in an antigen-specific manner during pregnancy.

ASRI2005-88

Comparable levels of CD4+CD25+ CTLA4+ Treg cells in peripheral blood of pre-eclampsia and normal pregnant patients S Paeschke1, N Horn1, C Fotopoulou2, A ZambonBertoja1, A Sollwedel1, ML Zenclussen1, P Casalis1, J Dudenhausen2, HD Volk1, F Chen2, A Zenclussen1 1

Institute for Medical Immunology, Charite, Medical University of Berlin, Germany, CVK and CCM; 2Department of Obstetrics and Gynecology, Charite, Medical University of Berlin, Germany, CVK

The acceptance of the semiallogeneic fetus within the maternal environment requires tolerance mechanisms not fully characterized yet. Normal pregnancy is known to be associated with a Th2 profile. Furthermore, T-regulatory cells were proposed to regulate the Th2/Th1 balance at early stages of pregnancy. Treg

American Journal of Reproductive Immunology 54 (2005) 120–123 ª 2005 Blackwell Munksgaard

ABSTRACTS

may avoid the shift to a Th1 profile preventing miscarriage. Accordingly, spontaneous abortion is characterized by a Th1 dominance and diminished levels of Tregulatory cells (Treg). The major aim of the present work was to investigate if pre-eclampsia, a late immunological complication of pregnancy, is characterized by similar hallmarks. Therefore, we measured the surface antigens CD4, CD25, CD8, CTLA4 (as well as the secretion of IL-10) in peripheral blood from patients suffering from pre-eclampsia (n = 8) and age-matched patients undergoing normal pregnancies (n = 9) by 4-colour flow-cytometry. We were not able to find any significant differences in the levels of CD4+, CD25+, CD8+, CTLA4, CD4+/CD25+, CD4+/CD25bright, CD4+/CTLA4, CD25+/CTLA4, CD4+/CD25+/CTLA4, CD8+/CD25+, CD8+/CTLA4 or CD8+/CD25+/CTLA4 cell subsets. Our data suggest that Treg may not participate in the onset of pre-eclampsia and suggest other regulatory mechanisms during late pregnancy.

observed. Surprisingly, after therapy the decidual levels of the Th1 cytokines IFN-c and TNF-a were not diminished. The transfer of Treg dramatically upregulated the expression of LIF, TGF-b and HO-1 at the fetal-maternal interface. Our data suggest that Treg-treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.

ASRI2005-90

Vaginal formulations – how innocuous are they to the vaginal epithelial immune function? RT Trifonova, J-M Pasicznyk, RN Fichorova Laboratory of Genital Tract Biology, Department of Obstetrics Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

ASRI2005-89

During pregnancy, treg cells induce a privileged tolerant microenvironment at the fetal-maternal interface by up-regulating HO-1, TGF-b and LIF expression ML Zenclussen, A Zambon Bertoja, K Gerlof, S Ritschel, A Sollwedel, HD Volk, AC Zenclussen Reproductive Immunology Group, Institute of Medical Immunology, Charite´, Medical University of Berlin, Germany

The mechanisms underlying immune tolerance during pregnancy are poorly understood. We recently proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus, since we observed diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. We transferred mice undergoing abortion with Treg from mice having normal pregnancies, including normal pregnant and abortion-prone mice as controls. We evaluated decidual lymphocytes for their cytokine profile. The mRNA levels for several tolerance-associated cytokines were also analyzed. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Locally, augmented foxp3 levels could be

Problem: The disruption of the epithelial barrier and activation of inflammatory pathways may lead to increased susceptibility to viral infection. Over-thecounter (OTC) vaginal products have received little attention in this regard, however the recent development of anti-HIV-1 microbicides has brought the importance of mucosal integrity to forefront. While vaginal microbicides represent a promising strategy for preventing HIV-1 and other sexually transmitted infections, they can be efficacious only if they cause no epithelial toxicity or inflammation. Method: We used a novel organotypic cervicovaginal model (VEC100, Mattek) to compare hygienic or spermicidal OTC to the anti-HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP). Results: CAP film and gel formulations appeared non-toxic in MTT and LDH viability assays and did not induce release of pro-inflammatory mediators e.g. IL-1, IL-6 and IL-8 as compared to controls. In contrast, a commercially available vaginal cleansing film containing Nonoxynol-9 showed proinflammatory potential commeasurable to that of TNFa. Conclusions: Our study demonstrates the usefulness of the VEC tissue model for immunoinflammatory characterization and safety assessment of vaginal products. It provides evidence that CAP in film and gel forms may be used as a safe anti-HIV-1 prevention agent or vehicle for other vaginal products. This study was supported by NICHD 1P01HD041761.

American Journal of Reproductive Immunology 54 (2005) 120–123 ª 2005 Blackwell Munksgaard

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ABSTRACTS

ASRI2005-91

Reduced semen quality in chronic prostatitis patients that have cellular autoimmune response to prostate antigens RM Motrich1, M Maccioni1, R Molina2, A Tissera2, JJ Olmedo3, CM Riera1, VE Rivero1 1

Centro de Investigaciones en Bioquı´mica Clı´nica e Inmunologı´a (CIBICI) CONICET. Facultad de Ciencias Quı´micas, Universidad Nacional de Co´rdoba, Co´rdoba, Argentina; 2LAR, Laboratorio de Andrologı´a y Reproduccio´n, Co´rdoba, Argentina; 3FUCDIM, Fundacio´n Urolo´gica Co´rdoba para la Docencia e Investigacio´n Me´dica

Problem: Acute and chronic infectious prostatitis (CIP) are the best understood of the prostate syndromes but the least frequent. In contrast, although chronic non-infectious prostatitis (CNIP) is the most frequent syndrome, its cause has proved elusive for decades. Method of study: In the present study we analyzed the presence of a possible autoimmune response to prostate antigens (PA) in patients with CIP and CNIP. We also analyzed their semen quality (spermiograms) and levels of seminal inflammatory cytokines. Results: We demonstrated the presence of lymphocytes able to proliferate in response to human PA (PSA and PAP) only in a group of patients with CNIP. When INFc and IL-10 levels were measured in culture supernatants, significantly elevated levels of INFc were detected only in patients with positive proliferative response to PA. Interestingly, only these patients showed significantly elevated levels of inflammatory cytokines (IL-1 and TNF-a) in seminal plasma and striking alterations in their semen quality. Conclusions: We found that INFc-secreting lymphocytes specific to PA are detected in 34% of the patients with CNIP and that this fact is associated with a marked alteration of semen quality. These results argue in favor of the importance of prostate functionality for the quality of the semen.

ASRI2005-92

Possible reproductive immunological importance of pp13 / galectin-13, a galectin with principally placental expression NG Than1, R Magenheim1, J Dienes1, T Kovacs1, B Nagy1, P Hupuczi1, H Meiri2, H Bohn3, Z Papp1

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1 1st Department of Obstetrics & Gynecology, Semmelweis University, Budapest, Hungary; 2Diagnostic Technologies Ltd., Haifa, Israel; 3 Behringwerke AG, Marburg/Lahn, Germany

As previous sequential and structural analyses showed its conserved homology to members of the galectin superfamily, Placental Protein 13 (PP13) was designated galectin-13. Similarly to eosinophil Charcot Leyden Crystal protein / galectin-10, its weak lysophospholipase activity was proved. Sugar binding assays revealed that residues widely expressed in placenta had the strongest binding affinity to PP13, which expression was found to be restricted to placenta. With regard to its strong labeling of the syncythiotrophoblasts’ brush border membrane as well as its co-localization and specific binding to annexin II, PP13 was assumed to be externalized to the cell surface like other galectins. In a comparative study we found, that in the 3rd trimester, expression of PP13 was significantly reduced in preeclamptic (n = 20) and HELLP syndrome (n = 5) placentas compared to gestational age matched healthy samples (n = 25). In the same pathologic cases, maternal PP13 serum levels were also lower than in controls. Recently, PP13 was also successfully tested as a new 1st and 2nd trimester placental marker for the prediction of preeclampsia and IUGR. With regard to these results, PP13 may have special immunobiological function at the lining of the common feto-maternal blood-paces. The possible clinical importance of PP13 in pathological pregnancies with immunological background have to be emphasized.

ASRI2005-93

A new aspect of reproduction in infertility associated with polcystic ovarian syndrome V Mehrotra1, P Saini2 1

Department of Biochemistry, HIMS; 2Saini Infertility Center, Dehradun, India

Introduction: Polycystic ovarian syndrome (PCOS) is one of the commonest causes of anovulatory infertility presenting with menstrual abnormalities. The common treatment is to ovulate and conceive is Clomiphene citrate but 50% becomes pregnant with first trimester abortion rate high. The aim is for better judgment of efficacy of Clomiphene citrate and recombinant FSH for ovulation induction.

American Journal of Reproductive Immunology 54 (2005) 120–123 ª 2005 Blackwell Munksgaard

ABSTRACTS

Method: Patients (120) were divided in two groups: treated with Clomiphene citrate and other on recombinant FSH. Ovarian response was monitored and HCG given to trigger ovulation after appropriate follicular development. The prime out come major cumulative pregnancies after undergoing up to 4 treatment cycles. Results: The study showed that aspects of reproduction with pregnancy rate were more in recombinant FSH as compare to clomiphene citrate. Abortion rate was less in recombinant FSH then clomiphene citrate group. The incidences of OHSS were least in both. The main aspects of repro-

duction after 4-treatment cycle were 45.8% with recombinant FSH and only 11.2% with Clomiphene citrate. Conclusions: Various RCTs have been done before showing benefits of Gonadotrophins over Clomiphene citrate. Study suggests that recombinant FSH effective alternative of Clomiphene citrate in first line treatment for the reproduction of anovulatory PCOS patients.

American Journal of Reproductive Immunology 54 (2005) 120–123 ª 2005 Blackwell Munksgaard

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