Study on γδT-Cell Degranulation at Maternal-Fetal Interface via iKIR-HLA-C Axis

Area of Science:

• Immunology
• Reproductive Biology
• Cellular Biology

Background:

• Maternal-fetal tolerance is vital to prevent immune rejection of the embryo during human pregnancy.
• Natural Killer (NK) cell cytotoxicity is inhibited by killer-cell immunoglobulin-like receptors (iKIR) binding to HLA-C molecules on target cells.

Purpose of the Study:

• To investigate the expression of iKIRs (KIR2DL1 and KIR2DL2/3) on decidual and peripheral γδT cells.
• To examine the localization of HLA-C ligands throughout human pregnancy.
• To evaluate the degranulation of γδT cells in pregnant and non-pregnant women when exposed to trophoblast cells.

Main Methods:

• Flow cytometry to assess iKIR expression on decidual and peripheral γδT cells.
• Immunohistochemistry to determine HLA-C expression in placental tissues.
• Degranulation assays using γδT cells and trophoblast cell lines (Sw71 EVT-like cells).

Main Results:

• A higher proportion of iKIR-positive γδT cells were found at the maternal-fetal interface in early pregnancy compared to peripheral blood and late pregnancy decidua.
• HLA-C expression was intense on intermediate cytotrophoblasts and invading extravillous trophoblasts (EVTs) in early pregnancy, diminishing in late pregnancy.
• Decidual γδT cells exhibited higher spontaneous degranulation than peripheral γδT cells in early pregnancy, but trophoblast cells did not modulate this degranulation.

Conclusions:

• The maternal-fetal interface in early pregnancy features increased iKIR-positive γδT cells and HLA-C expression, suggesting a role in immune regulation.
• Trophoblast cells do not effectively suppress γδT cell cytotoxicity, indicating that maternal-fetal tolerance involves mechanisms beyond simple NK-like inhibition.