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-gamma-producing lymphocytes in response to alloantigen in an ELISPOT assay and higher IFN-gamma 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.
authors: Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. indira.guleria@tch.harvard.edu
authors: Indira
authors: I
authors: Guleria
authors: Arezou
authors: A
authors: Khosroshahi
authors: Mohammed Javeed
authors: MJ
authors: Ansari
authors: Antje
authors: A
authors: Habicht
authors: Miyuki
authors: M
authors: Azuma
authors: Hideo
authors: H
authors: Yagita
authors: Randolph J
authors: RJ
authors: Noelle
authors: Anthony
authors: A
authors: Coyle
authors: Andrew L
authors: AL
authors: Mellor
authors: Samia J
authors: SJ
authors: Khoury
authors: Mohamed H
authors: MH
authors: Sayegh
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D060890:B7-H1 Antigen; D005260:Female; D005327:Fetal Resorption / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D018417:Th1 Cells / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; C064658:RAG-1 protein; D007371:Interferon-gamma