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

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.