Hdl Handle:
http://hdl.handle.net/10675.2/558
Title:
A critical role for the programmed death ligand 1 in fetomaternal tolerance
Authors:
Guleria, Indira; Khosroshahi, Arezou; Ansari, Mohammed Javeed; Habicht, Antje; Azuma, Miyuki; Yagita, Hideo; Noelle, Randolph J.; Coyle, Anthony; Mellor, Andrew L.; Khoury, Samia J.; Sayegh, Mohamed H.
Abstract:
Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell– but not B cell–dependent because PDL1-specific antibody treatment caused fetal rejection in B cell–deficient but not in RAG-1 –deficient females. Blockade of PDL1 also resulted in a significant increase in the frequency of IFN- –producing lymphocytes in response to alloantigen in an ELISPOT assay and higher IFN- levels in placental homogenates by ELISA. Finally, PDL1-deficient females exhibited decreased allogeneic fetal survival rates as compared with littermate and heterozygote controls and showed evidence of expansion of T helper type 1 immune responses in vivo. These results provide the first evidence that PDL1 is involved in fetomaternal tolerance.
Citation:
J Exp Med. 2005 Jul 18; 202(2):231-237
Issue Date:
18-Jul-2005
URI:
http://hdl.handle.net/10675.2/558
DOI:
10.1084/jem.20050019
PubMed ID:
16027236
PubMed Central ID:
PMC2213002
Type:
Article
ISSN:
1540-9538
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorGuleria, Indiraen_US
dc.contributor.authorKhosroshahi, Arezouen_US
dc.contributor.authorAnsari, Mohammed Javeeden_US
dc.contributor.authorHabicht, Antjeen_US
dc.contributor.authorAzuma, Miyukien_US
dc.contributor.authorYagita, Hideoen_US
dc.contributor.authorNoelle, Randolph J.en_US
dc.contributor.authorCoyle, Anthonyen_US
dc.contributor.authorMellor, Andrew L.en_US
dc.contributor.authorKhoury, Samia J.en_US
dc.contributor.authorSayegh, Mohamed H.en_US
dc.date.accessioned2012-10-26T16:26:40Z-
dc.date.available2012-10-26T16:26:40Z-
dc.date.issued2005-07-18en_US
dc.identifier.citationJ Exp Med. 2005 Jul 18; 202(2):231-237en_US
dc.identifier.issn1540-9538en_US
dc.identifier.pmid16027236en_US
dc.identifier.doi10.1084/jem.20050019en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/558-
dc.description.abstractFetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell– but not B cell–dependent because PDL1-specific antibody treatment caused fetal rejection in B cell–deficient but not in RAG-1 –deficient females. Blockade of PDL1 also resulted in a significant increase in the frequency of IFN- –producing lymphocytes in response to alloantigen in an ELISPOT assay and higher IFN- levels in placental homogenates by ELISA. Finally, PDL1-deficient females exhibited decreased allogeneic fetal survival rates as compared with littermate and heterozygote controls and showed evidence of expansion of T helper type 1 immune responses in vivo. These results provide the first evidence that PDL1 is involved in fetomaternal tolerance.en_US
dc.rightsCopyright © 2005, The Rockefeller University Pressen_US
dc.subjectBrief Definitive Reporten_US
dc.titleA critical role for the programmed death ligand 1 in fetomaternal toleranceen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2213002en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-

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