title: Human decidual macrophages suppress IFN-γ production by T cells through costimulatory B7-H1:PD-1 signaling in early pregnancy.
abstract: In human pregnancy, CD14⁺ decidual macrophages (DMs) are the dominant professional antigen-presenting cells in the decidua, comprising 20-30% of the local leukocyte population. Although the relevance of DMs to feto-maternal immune tolerance has been described, the molecular mechanisms underlying these functions have not been fully elucidated. B7-H1, a costimulatory ligand in the B7 family, negatively modulates T cell activity by binding to its corresponding receptor, PD-1. The present study aimed to investigate the functional significance of costimulatory interactions between DMs and T cells, with a particular focus on B7-H1:PD-1 signaling. An analysis of the expression profile of B7 ligands on human DMs revealed that B7-H1 was present on DMs isolated from early but not term pregnancies. B7-H1 was not expressed on the peripheral monocytes (PMs) of pregnant women. In response to IFN-γ, B7-H1 expression was induced on PMs and was enhanced on DMs, suggesting that this cytokine might be a key factor in the control of B7-H1 expression in the decidua. The majority of decidual T cells were noted to exhibit robust expression of PD-1, whereas the expression was limited to a small subpopulation of circulating T cells. Functional assays demonstrated that DMs are able to suppress T cell IFN-γ production via B7-H1:PD-1 interactions. This suppressive property was not observed for PMs, which lack B7-H1. B7-H1 on DMs may function as a key regulator of local IFN-γ production and thereby contribute to the development of appropriate maternal immune responses to the fetus in early pregnancy.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Sayama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagamatsu
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Schust
authors.forename: Naoko
authors.initials: N
authors.lastname: Itaoka
authors.forename: Mayuko
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Shiro
authors.initials: S
authors.lastname: Kozuma
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D011247:Pregnancy; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D018950:Lipopolysaccharide Receptors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
keywords: B7-H1; Costimulation; Decidual macrophage; Human pregnancy