Placental trophoblast from successful human pregnancies expresses the tolerance signaling molecule, CD200 (OX-2)

PROBLEM: Th1 cytokine-dependent abortions in the CBA x DBA/2 mouse model have been linked to down-regulation of expression of the CD200 (OX-2) 'tolerance' signal on trophoblast and in decidua prior to onset of the abortion process. Abortions could be prevented by, administration of a soluble CD200. Is CD200 expressed on trophoblast in successful human pregnancy? METHOD OF STUDY: As one cannot easily obtain trophoblasts in large quantities from successful human pregnancies in the first trimester prior to the onset of the abortion process at 6 weeks gestation, we examined as a first step, trophoblast isolated from term placentae (i.e. successful pregnancies). CD9(-) trophoblasts were isolated by affinity column and stained for intracellular cytokeratin, and surface CD200 using PE-anti-human CD200 monoclonal antibody. mRNA was extracted from CD9(+) and CD9(-) cells and tested by reverse transcription-polymerase chain reaction for CD200 mRNA. CD9(-) placental cells were separated by velocity sedimentation and test for CD200-dependent suppression of an allogeneic human mixed lymphocyte culture where cytotoxic T cell (CTL) generation, and Th1 --> Th2 cytokine production shift were measured. RESULTS: CD9(-) but not CD9(+) placental cell populations contained cells with mRNA for CD200, both a normal length transcript and a truncated transcript. Flow cytometry showed a CD200(+) cytokeratin(+) moderate-to-large-sized cell population compatible with trophoblasts and a smaller subset of cytokeratin(-) cells that expressed CD200 at normal and at high levels. The moderate-sized population proved most potent at inhibiting CTL generation and caused a Th1 --> Th2 cytokine shift. These effects were blocked by monoclonal anti-CD200. CONCLUSIONS: A subpopulation of cytokeratin(+) placental trophoblasts express bioactive CD200 able to alter maternal immune responses in a favorable (Th2 > Th1) direction. Two populations of CD200(+) small- and medium-small-sized cytokeratin(-) placental cells remain to be identified. Studies of karyotyped first trimester elective termination and spontaneous miscarriage tissues are needed.