Placental extravillous cytotrophoblasts persistently express class I major histocompatibility complex molecules after human cytomegalovirus infection.

Human cytomegalovirus (HCMV) downregulates the class I major histocompatibility complexes (MHCs), HLA-A and -B, in infected fibroblasts to escape from antigen-specific cytotoxic T lymphocytes. The HCMV genes responsible for the downregulation of MHCs are US2, US3, US6, and US11, which encode type I membrane proteins working at the endoplasmic reticulum (ER). However, it is largely unknown whether HCMV downregulates the class I MHC molecules in placental extravillous cytotrophoblasts (EVT), which express HLA-C, -E, and -G to protect a semiallogenic fetus from maternal natural killer (NK) cells at the fetomaternal interface. Here, we report that differentiated EVT prepared from human first-trimester chorionic villi persistently express class I MHC molecules upon HCMV infection. When these US proteins were expressed in uninfected EVT, they were localized at the ER in the entire cytoplasm. However, subsequent HCMV infection resulted in dissociation of these US proteins from the ER, which relocated toward the cell membrane. In fibroblasts, these US proteins were localized at the ER before and after HCMV infection. These results suggest that the US gene products are not integrated into ER of HCMV-infected EVT and fail to downregulate class I MHC molecules.

Accumulation of CD16+ cells with secretion of Ksp37 in decidua at the end of pregnancy.

PROBLEM: Maternal cellular immunity is thought to be in a state of tolerance during pregnancy, but the precise mechanism of immunomodulation is not yet known. We investigated a novel serum protein, killer-specific secretory protein of 37 kDa (Ksp37), produced by cytotoxic lymphocytes, during pregnancy. METHOD OF STUDY: The level of Ksp37 was determined by enzyme linked immunosorbent assay (ELISA) in the sera of healthy pregnant women. Intracellular Ksp37 expression in mononuclear cells, isolated from peripheral blood and decidua at parturition, was examined with a flow cytometer. RESULTS: Serum Ksp37 levels significantly increased at late pregnancy, compared with non-pregnant controls and the first trimester of pregnancy. The flow cytometric analysis exhibited that Ksp37 was mainly expressed in CD16+ natural killer (NK) cells in decidua of term placenta. CONCLUSIONS: Serum Ksp37 level was elevated at late gestational period. CD16+ NK cells in decidua seem to be a main maternal source of Ksp37. Innate immunity, with CD16+ NK cells, may play important roles near parturition.