Villitis of unknown etiology is associated with major infiltration of fetal tissue by maternal inflammatory cells

Abstract

Villitis of unknown etiology (VUE) is a common placental lesion and an important cause of intrauterine growth retardation and recurrent reproductive failure. Two theories have been proposed to explain VUE. One proposes that VUE is an exclusively fetal immune response to microbial antigen, whereas the other suggests that maternal cells cross the maternal-fetal interface and mount an immune response to fetal antigens. To differentiate between these alternatives, we performed in situ hybridization using X and Y chromosome-specific probes and immunostaining for CD3 and CD45 on VUE placentas from male infants. A total of eight foci and 40 villi were studied from four male VUE placentas. Controls included nonaffected villi from each male VUE placenta, a female VUE placenta, and male and female tonsils. Affected villi showed a major proportion of XX (maternal) cells (range 30 to 54%). An appropriate percentage of the remaining (fetal) cells contained Y chromosomes. The fraction of cells within the eight foci staining for CD3 (T lymphocytes) ranged from 34 to 57%, whereas the fraction staining for CD45/LCA (total leukocytes) ranged from 45 to 74%. The proportion of maternal cells within each focus was significantly correlated with the number of CD3-positive T lymphocytes but not with the number of CD3-negative leukocytes. We conclude that maternal cells, probably CD3-positive T cells, cross the maternofetal barrier and participate in VUE.