Cell-specific expression of B lymphocyte (APRIL, BLyS)- and Th2 (CD30L/CD153)-promoting tumor necrosis factor superfamily ligands in human placentas.
Human placentae and two of the cell types in placentae (cytotrophoblasts and macrophages) were examined by RT-PCR for transcripts of the eight TNF superfamily ligands known to induce death of activated immune cells, tumour cells, and virus-infected cells (TNFalpha, LT alpha, LT beta, FasL, TRAIL, TWEAK, LIGHT, 4-1BBL). Transcripts for all ligands were detected in term placenta but LT alpha and 4-1BBL were not detected in first trimester placenta. Although term cytotrophoblasts contained mRNAs specific for TNF alpha, LT alpha, TWEAK, and 4-1BBL, messages encoding LT beta, FasL, TRAIL, and LIGHT were absent. In term placental macrophages, messages for all ligands except 4-1BBL were present. Transcripts for the 14 receptors to which the ligands bind, six of which contain death-domains (TNFR1, Fas, DR3, DR4, DR5, DR6), were also identified using RT-PCR. Term and first trimester placentae contained transcripts for all receptors except 4-1BB. Although term cytotrophoblasts lacked receptor mRNA encoding 4-1BB and OPG, term placental macrophages lacked DcR1 and OPG. Detection of nearly all the death-inducing TNF superfamily ligands and their receptors in human placentae implies that these powerful cytokines contribute to programmed or activated cell death in this organ.