Upregulation of decidual P-selectin expression is associated with an increased number of Th1 cell populations in patients suffering from spontaneous abortions.
A multicascade of leukocyte-endothelial cell interactions is involved in the trafficking of inflammatory lymphocytes into tissue. The primary contact between leukocytes and endothelium is mediated by selectins. Ligands for P-Selectin are preferentially expressed on Th1 cells and thereby allow migration of these inflammatory cells through the vessel wall. Since a peripheral and local Th1-type cytokine profile is present in spontaneous human abortion (SA), opposed by a Th2 dominant situation in normal pregnancies (NP), we investigated (1) the phenotype of peripheral Th1 cells by flow cytometry, as well as the Th1-type cytokine levels by ELISA, (2) the decidual expression of P- and E-Selectin by immunohistochemistry (IHC), and (3) the phenotype of decidual immunocompetent cells by IHC in patients with NP or SA. We observed enhanced production of IFN-gamma and TNF-alpha in CD8(+), CD3(+), and CD56(+) blood cells, as well as an increase in the number of CCR5(+) cells in patients suffering from SA compared to those with NP. No difference was detectable with respect to the serum levels of the two cytokines. Using IHC methods, we observed increased staining intensity of P-Selectin(+) vessels in samples of SA patients. E-Selectin was only weakly expressed in decidual endothelial cells, with no difference between NP and SA. In SA samples, E-Selectin(+) stromal cells were exclusively present. We further detected increased numbers of decidual CD8(+), CD3(+), CCR5(+), and CD56(+) cells in SA patients. We propose that Th1 lymphocyte migration into decidua is enhanced in SA due to upregulated P-Selectin expression in decidual vessels. This increase of Th1-producing lymphocytes might be involved in the rejection of trophoblasts.
Zenclussen
A C
AC
Department of Medicine, Humboldt University, Berlin, Germany.
Fest
S
S
Sehmsdorf
U S
US
Hagen
E
E
Klapp
B F
BF
Arck
P C
PC
D000022:Abortion, Spontaneous / Q000097:blood / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D017252:CD3 Complex / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D019040:E-Selectin / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007121:Immunocompetence; D007371:Interferon-gamma / Q000097:blood; D018655:Lymphocyte Count; D019007:P-Selectin / Q000096:biosynthesis*; D011247:Pregnancy; D019713:Receptors, CCR5 / Q000276:immunology; D018417:Th1 Cells / Q000145:classification / Q000166:cytology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015854:Up-Regulation
D015415:Biomarkers; D017252:CD3 Complex; D019002:CD56 Antigen; D016827:CD8 Antigens; D019040:E-Selectin; D019007:P-Selectin; D019713:Receptors, CCR5; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma