Background/Aims: Tolerance of T lymphocytes at the feto-maternal interface is necessary to sustain normal pregnancy. The present investigation aimed to observe the regulatory effects on T lymphocytes by human trophoblasts and to explore possible effector molecules. Methods: Conditioned media was made by trophoblast culture or villous explant culture for T lymphocyte proliferation and proteomic analysis. Lymphocyte proliferation was tested by thymidine incorporation. Messenger RNA for indoleamine 2,3- dioxygenase (IDO) was detected by RT-PCR and tryptophan was assayed. The protein profile of conditioned media was assessed with shotgun mass-spectrometry and the identified proteins were bioinformatically analyzed. Human chorionic gonadotropin (HCG), human chorionic somatomammotropin (HCS), interleukin (IL)-2, 4, 10 and tumor necrosis factor (TNF)- α were assayed with radioimmunoassay (RIA). Results: T Lymphocyte proliferation was inhibited by conditioned medium in a dose-dependant manner. Inhibition of IDO during previous conditioning or addition of tryptophan to the conditioned medium partly restored T lymphocyte proliferation. mRNA for IDO was expressed in trophoblasts and chorionic villi. The concentrations of tryptophan were 19.01 and 3.79 µmol/L in unconditioned and conditioned media respectively. By proteomic procedures, 548 proteins were found in placenta-conditioned medium. Among these proteins were some proteins inhibiting T lymphocytes including HCG, HCS, AFP, pregnancy-specific beta 1-glycoprotein (SP1), glycodelin, transforming growth factor β2, thrombospondin-1, pigment epithelium-derived factor (PEDF), galectin-1, and macrophage migration inhibitory factor. HCG and HCS were also detected with RIA, however, no interleukins were detected in conditioned media with RIA or proteomic analysis. Conclusions: Trophoblasts inhibit T lymphocyte through IDO-mediated tryptophan depletion and placenta-derived immunoregulatory factors. Immunological tolerance at maternal-fetal interface represents a synergistic effect of these substances and a complex mechanism involving endocrine and immune networks.
Womens Hospital, School of Medicine, Zhejiang University
2 Xueshi Road, Hangzhou, Zhejiang Province,310006 (China)
Tel. +86 571 8820 8007, Fax: +86 571 8706 1878
Accepted: January 21, 2008
Published online: April 24, 2008
Number of Print Pages : 10
Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)
Vol. 21, No. 5-6, Year 2008 (Cover Date: 2008)
Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)
For additional information: http://www.karger.com/journals/cpb
Copyright / Drug Dosage
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.