Secretion of pro-apoptotic intron 4-retaining soluble HLA-G1 by human villous trophoblast.
One major materno-fetal interface in the human placenta is constituted by the syncytiotrophoblast, in contact with maternal blood of the intervillous space, which derives from differentiation and fusion of the villous cytotrophoblast (vct). In the present work, we purified vct from term placenta by depleting HLA class I- and class II-positive cells. We found by RT-PCR that both soluble intron 4-retaining HLA-G1 (sHLA-G1) and HLA-G2 isoforms were transcribed in purified vct. Using different HLA-G-specific mAb, we demonstrated by intracellular flow cytometry, Western blotting and ELISA, that sHLA-G1 but no soluble HLA class Ia molecule was secreted by vct. We then purified sHLA-G1 from vct culture supernatant and found that it exhibited an unusual glycosylation pattern. Finally, we showed that such trophoblast-derived sHLA-G1 triggered specific apoptosis of activated CD8+ T cells. Taken together, these results demonstrated that vct did secrete functional sHLA-G1 in primary culture and suggested that, in vivo, sHLA-G1 might be an important immunomodulatory molecule controlling the activity of maternal immune effector CD8+ cells circulating in the blood that immerses chorionic villi.
Solier
Corinne
C
INSERM U563, Hôpital Purpan, Toulouse, France.
Aguerre-Girr
Maryse
M
Lenfant
Françoise
F
Campan
Agnès
A
Berrebi
Alain
A
Rebmann
Vera
V
Grosse-Wilde
Hans
H
Le Bouteiller
Philippe
P
D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006031:Glycosylation; D006680:HLA Antigens / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007438:Introns; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D014327:Trophoblasts / Q000276:immunology*
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I