Involvement of Hofbauer cells and maternal T cells in villitis of unknown aetiology

Abstract

Aims: The nature of villitis of unknown aetiology (VUE) is intriguing in terms of its aetiology, origin of inflammatory cells and immunophenotype of T cells involved. The aim was to determine the origin of macrophages and the immunophenotype of T lymphocytes in VUE associated with various complications of pregnancy.

Methods and results: Placentas with VUE (n = 45) were studied by chromogenic in-situ hybridization (CISH) for Y chromosome (DYZ1) and immunohistochemistry for CD14, CD68, Ki67 (n = 10; all from male neonates) and a panel of T-cell antigens (CD3, CD4 and CD8) (n = 35). All of the placentas from male neonates showed CISH+ signals from Y chromosomes in the majority of macrophages, but not in lymphocytes, indicating that the macrophages were of fetal origin. Many macrophages of the affected chorionic villi were Ki67+, suggesting that they are hyperplastic Hofbauer cells. Among the lymphocytes, CD8+ T cells outnumbered CD4+ T cells in all placentas with different obstetrical conditions.

Conclusions: We define primary components of VUE as maternal CD8+ T cells and hyperplastic Hofbauer cells. We propose that VUE is a unique inflammatory reaction where the leucocytes from two hosts are key partners, analogous to either allograft rejection or graft-versus-host disease.

Figure 1

A, Double staining for CD14 (brown) and CD68 (blue) detects an increased number of macrophages in the villitis of unknown etiology (VUE)-affected area. B, Chromogenic in-situ hybridization using a Y chromosome-specific probe (DYZ1) shows that a majority of the macrophages have a distinct intranuclear hybridization signal indicating that they are of fetal origin, whereas intervillous mononuclear inflammatory infiltrates of maternal origin are consistently negative (right upper part). C, VUE-affected areas are easily recognized by prominent Ki67 immunoreactivity in the inflammatory cells of the villous stroma (right side), when compared with unaffected areas (left side). D, Double immunohistochemistry for Ki67 (brown) and CD68 (blue) shows proliferating macrophages with Ki67 nuclear labeling (arrowheads).

Figure 2

Immunohistochemical features of villitis of unknown etiology (VUE) taken from two representative cases (case 1 and case 2). Necrotizing villous inflammation is present in both cases. Immunohistochemistry for a panel of T-cell antigens shows that the majority of infiltrating CD3+ T cells is positive for CD8. CD4+ T cells are sparsely distributed.