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

Indira Guleria, Arezou Khosroshahi, Mohammed Javeed Ansari, Antje Habicht, Miyuki Azuma, Hideo Yagita, Randolph J. Noelle, Anthony Coyle, Andrew L. Mellor, Samia J. Khoury, Mohamed H. Sayegh

Research output: Contribution to journalArticle

253 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)231-237
Number of pages7
JournalJournal of Experimental Medicine
Volume202
Issue number2
DOIs
StatePublished - Jul 18 2005

Fingerprint

Ligands
Isoantigens
Pregnancy
B-Lymphocytes
T-Lymphocytes
Enzyme-Linked Immunospot Assay
Heterozygote
Enzyme-Linked Immunosorbent Assay
Mothers
Lymphocytes
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Guleria, I., Khosroshahi, A., Ansari, M. J., Habicht, A., Azuma, M., Yagita, H., ... Sayegh, M. H. (2005). A critical role for the programmed death ligand 1 in fetomaternal tolerance. Journal of Experimental Medicine, 202(2), 231-237. https://doi.org/10.1084/jem.20050019

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

In: Journal of Experimental Medicine, Vol. 202, No. 2, 18.07.2005, p. 231-237.

Research output: Contribution to journalArticle

Guleria, I, Khosroshahi, A, Ansari, MJ, Habicht, A, Azuma, M, Yagita, H, Noelle, RJ, Coyle, A, Mellor, AL, Khoury, SJ & Sayegh, MH 2005, 'A critical role for the programmed death ligand 1 in fetomaternal tolerance', Journal of Experimental Medicine, vol. 202, no. 2, pp. 231-237. https://doi.org/10.1084/jem.20050019
Guleria I, Khosroshahi A, Ansari MJ, Habicht A, Azuma M, Yagita H et al. A critical role for the programmed death ligand 1 in fetomaternal tolerance. Journal of Experimental Medicine. 2005 Jul 18;202(2):231-237. https://doi.org/10.1084/jem.20050019
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. / A critical role for the programmed death ligand 1 in fetomaternal tolerance. In: Journal of Experimental Medicine. 2005 ; Vol. 202, No. 2. pp. 231-237.
@article{5e6b75cde522488a9d969a59a804a5d1,
title = "A critical role for the programmed death ligand 1 in fetomaternal tolerance",
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.",
author = "Indira Guleria and Arezou Khosroshahi and Ansari, {Mohammed Javeed} and Antje Habicht and Miyuki Azuma and Hideo Yagita and Noelle, {Randolph J.} and Anthony Coyle and Mellor, {Andrew L.} and Khoury, {Samia J.} and Sayegh, {Mohamed H.}",
year = "2005",
month = "7",
day = "18",
doi = "10.1084/jem.20050019",
language = "English (US)",
volume = "202",
pages = "231--237",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - A critical role for the programmed death ligand 1 in fetomaternal tolerance

AU - Guleria, Indira

AU - Khosroshahi, Arezou

AU - Ansari, Mohammed Javeed

AU - Habicht, Antje

AU - Azuma, Miyuki

AU - Yagita, Hideo

AU - Noelle, Randolph J.

AU - Coyle, Anthony

AU - Mellor, Andrew L.

AU - Khoury, Samia J.

AU - Sayegh, Mohamed H.

PY - 2005/7/18

Y1 - 2005/7/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=22944436502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22944436502&partnerID=8YFLogxK

U2 - 10.1084/jem.20050019

DO - 10.1084/jem.20050019

M3 - Article

C2 - 16027236

AN - SCOPUS:22944436502

VL - 202

SP - 231

EP - 237

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 2

ER -