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A critical role for the programmed death ligand 1 in fetomaternal tolerance

Open access
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.·2005·The Journal of Experimental Medicine
DOI 10.1084/jem.20050019
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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-γ–producing lymphocytes in response to alloantigen in an ELISPOT assay and higher IFN-γ 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.

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Metadata

Authors
Guleria, I., Khosroshahi, A., Ansari, M. J., Habicht, A., Azuma, M., Yagita, H., Noelle, R. J., Coyle, A., Mellor, A. L., Khoury, S. J., & Sayegh, M. H.
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2005-07-18
Volume
202
Issue
2
Pages
231-237
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20050019
OpenAlex
W2098494951
Cited by
439
References
2
FWCI
7.30
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: A critical role for the programmed death ligand 1 in fetomaternal tolerance. https://app.cochat.ai/papers/10.1084/jem.20050019
The paper
Guleria, I., Khosroshahi, A., Ansari, M. J., Habicht, A., Azuma, M., Yagita, H., Noelle, R. J., Coyle, A., Mellor, A. L., Khoury, S. J., & Sayegh, M. H. (2005). A critical role for the programmed death ligand 1 in fetomaternal tolerance. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20050019

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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