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 journalArticlepeer-review

278 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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