A Commentary on Gestational Programming and Functions of HLA-G in Pregnancy

Gestational programming of Paan-AG messages in the olive baboon. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to investigate Paan-AG transcripts in the olive baboon blastocyst, zygote and oocyte. The positive control was an extract of baboon placenta. All RNAs were acquired at the University of Illinois – Chicago (A.T. Fazleabas). Note that mRNA encoding the single soluble isoform of Paan-AG, Paan-AG5, is present at all stages. By contrast, Paan-AG1 mRNA, which encodes a membrane isoform, is detectable only in the placenta.

HLA-G and β2m proteins expressed by trophoblast cells in the early to middle gestation placental villus, trophoblastic column, trophoblastic shell and decidua. Although only HLA-G5 has been reported as positive in precursor cytotrophoblast cells and the proximal column, at least four isoforms (HLA-G1, -G2, -G5, -G6) and light chain, β2m, are expressed at the junction of the column and decidua as well as within the decidua. Revised and updated from Ref. [6], Fig. 4.

Multiple receptors for HLA-G are expressed on immune and other cells. Many types of cells that participate in immune responses express receptors for HLA-G, including CD4+ and CD8+T cells, B cells, NK cells, macrophages and dendritic cells. Newly added is the endothelial cell, which has been reported to bind HLA-G via CD160 [39]. Revised and updated from Ref. [4], Fig. 6.

Neither CD4 nor CD25 mRNA is altered in CD4+ cells following incubation with HLA-G5 or -G6. Mononuclear cells were harvested from healthy volunteers under a protocol approved by the Kansas Human Subjects Committee. CD4+ cells were selected by using magnetic bead technology. The cells were incubated in lymphocyte serum-free medium in the presence or absence (Control) of 50nM of recombinant HLA-G5 or -G5 [14] for 24h or 48h. RNA was isolated and subjected to RT-PCR to detect CD4 and CD25 mRNAs. Although all signals were stronger at 48h than at 24h, recombinant HLA-G5 and -G6 had no major effect on levels of CD4 or CD25 in the CD4+T lymphocytes. The negative control (water) yielded no signal.