An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage

Area of Science:

• Immunology
• Reproductive Medicine
• Cell Biology

Background:

• Recurrent miscarriage (RM) affects 1% of couples trying to conceive.
• Known causes like chromosomal aneuploidy do not explain all RM cases.
• An immunological etiology for RM is hypothesized, focusing on endometrial immune cells.

Purpose of the Study:

• To characterize the endometrial CD8-T cell population during the window of implantation.
• To investigate potential differences in these cells in women with unexplained RM compared to controls.

Main Methods:

• Characterization of endometrial CD8-T cells during the embryonic window of implantation.
• Analysis of CD8, CD69, CD103, and CD127 expression in T cells.
• Comparison of immune cell phenotype between women with RM and control women.

Main Results:

• The majority of endometrial CD8-T cells are tissue-resident memory T cells (TRM) expressing CD69 and CD103.
• Women with unexplained RM show significantly decreased expression of CD8 and CD69 on these cells.
• Endometrial CD8-T cells in RM patients exhibit reduced CD127 expression, indicating altered IL-7 signaling and homeostatic control.
• These altered immune cell phenotypes persist in the endometrium for over three months post-miscarriage.

Conclusions:

• This study provides the first evidence of a distinct pre-pregnancy phenotype in endometrial immune cells in women with RM.
• Altered CD8-T cell populations, characterized by reduced CD8 and CD69 expression and impaired homeostatic control, may contribute to the pathophysiology of unexplained recurrent miscarriage.