Expression and function of PDCD1 at the human maternal-fetal interface.
The failure to reject the semiallogenic fetus by maternal T lymphocytes suggests that potent mechanisms regulate these cells. PDCD1 is a CD28 family receptor expressed by T cells, and its ligand CD274 is strongly expressed by trophoblast cells of the human placenta. In this study, we examined whether human maternal T cells express PDCD1. Immunofluorescence examination of uterine tissues revealed PDCD1 expression on CD3+ cells was low in nonpregnant endometrium but increased in first-trimester decidua and remained elevated in term decidua (P < 0.05). In addition, higher relative proportions of term decidual CD8 bright, CD4+, and regulatory T cells expressed PDCD1 in comparison to autologous peripheral blood (P < 0.05). Term decidual T cells also expressed full-length and soluble PDCD1 mRNA isoforms more abundantly than their peripheral blood counterparts (P <or= 0.05). We also examined the effects of PDCD1:CD274 interactions in decidual T cells. Jar choriocarcinoma cells were transfected with CD274 and cocultured with activated decidual CD4+ or CD8 bright T cells for 72 h followed by analysis of cytokine concentration and decidual T cell apoptosis. Compared with empty vector-transfected cells, CD274-transfected Jar cells caused a significant suppression of interferon gamma and tumor necrosis factor alpha production by CD4+ (P < 0.05) but not CD8 bright T cells, while having no effect on secretion of IL10 or T cell apoptosis. These results suggest that the PDCD1:CD274 pathway functions in modification of maternal decidual lymphocyte cytokine secretion during pregnancy.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Elizabeth S
ES
Taglauer
Ann S
AS
Trikhacheva
Joyce G
JG
Slusser
Margaret G
MG
Petroff
D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D060890:B7-H1 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003656:Decidua / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011247:Pregnancy; D061026:Programmed Cell Death 1 Receptor; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D047929:Term Birth / Q000276:immunology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D020033:Protein Isoforms; D012333:RNA, Messenger