Regulatory KIR⁺CD8⁺ T cells are elevated during human pregnancy

Area of Science:

• Immunology
• Reproductive Immunology
• Cellular Immunology

Background:

• Maternal-fetal tolerance requires balancing immunity and acceptance of the semiallogeneic fetus.
• Mechanisms of maternal-fetal tolerance are not fully understood.
• Killer cell immunoglobulin-like receptor (KIR)+ CD8+ T cells regulate self-reactivity in other immune contexts.

Purpose of the Study:

• Investigate the role and activity of KIR+ CD8+ T cells during human pregnancy.
• Determine if KIR+ CD8+ T cells contribute to maternal-fetal tolerance.
• Explore the association of KIR+ CD8+ T cells with pregnancy outcomes.

Main Methods:

• Quantified KIR+ CD8+ T cells in peripheral blood and decidua during pregnancy.
• Performed in vitro assays to assess T cell alloreactivity inhibition.
• Utilized single-cell RNA sequencing of decidual T cells.
• Correlated KIR+ CD8+ T cell frequency with pregnancy outcomes like spontaneous abortion and preeclampsia.

Main Results:

• Increased frequency of KIR+ CD8+ T cells observed in the second trimester, especially with male fetuses.
• KIR+ CD8+ T cells suppressed maternal alloreactive T cells and CD8+ T cells targeting male-specific antigens in vitro.
• KIR+ CD8+ T cells expanded and differentiated into cytotoxic cells during pregnancy.
• Elevated KIR+ CD8+ T cells found in the decidua with increased activation markers.
• Higher KIR+ CD8+ T cell frequency associated with spontaneous abortion and preeclampsia.

Conclusions:

• KIR+ CD8+ T cells play a role in modulating fetal-specific alloreactive T cell responses, potentially contributing to maternal tolerance.
• The frequency of KIR+ CD8+ T cells may be influenced by fetal sex.
• KIR+ CD8+ T cells could serve as biomarkers or therapeutic targets for pregnancy disorders.