Ovarian localization drives IL-7R-dependent CD8 coreceptor expression in peripheral double-negative T cells

Area of Science:

• Immunology
• Reproductive Biology
• T cell Biology

Background:

• The ovary is immunologically active, balancing inflammation and T cell tolerance.
• It is unclear if the ovary instructs infiltrating lymphocytes or simply enriches existing subsets.

Purpose of the Study:

• To investigate if the ovary actively modifies the phenotype of infiltrating T cells.
• To identify the mechanisms behind ovarian immune cell conditioning.

Main Methods:

• Adoptive transfer of labeled splenic double-negative T cells (DNTs) into recipient mice.
• Analysis of DNT phenotype and localization in the ovary using flow cytometry and single-cell RNA-sequencing.
• In vitro co-culture assays with ovarian cells and DNTs.
• Assessment of IL-7 receptor (IL-7R) and IL-7 roles in DNT CD8 upregulation.

Main Results:

• Ovarian localization led to CD8 expression on transferred DNTs within 4 days.
• Ovarian cells in vitro induced CD8 upregulation on DNTs.
• Single-cell RNA-seq revealed IL-7-expressing stromal cells and IL-7R-enriched DNTs in the ovary.
• IL-7R signaling was essential for efficient CD8 induction on DNTs in the ovary.

Conclusions:

• The ovary acts as an immune-conditioning environment.
• Ovarian entry induces CD8 coreceptor expression on peripheral DNTs.
• IL-7R signaling is critical for this T cell phenotype modulation in the ovarian microenvironment.