<p>The ovary is an immunologically dynamic tissue that coordinates recurrent inflammation-like remodeling while preserving local T cell tolerance, yet whether it actively instructs infiltrating lymphocyte phenotype or passively enriches pre-existing subsets has not been directly tested. To address this, we used peripheral double-negative T cells (DNTs; CD3<sup>+</sup>CD4<sup>−</sup>CD8<sup>−</sup>NK1.1<sup>−</sup>) as a coreceptor-null system to detect tissue-imposed phenotypic change after ovarian entry. Using adoptive transfer, labeled splenic DNTs accumulated in the ovary relative to other tissue sites, and donor DNTs acquired surface CD8 expression within 4 days of ovarian localization. Dissociated ovarian cells were sufficient to drive CD8 upregulation on sorted DNTs in vitro, supporting that ovarian cellular cues can promote this response. Ovarian single-cell RNA-seq provided supportive evidence for <i>Il7</i>-expressing stromal subsets, and an <i>Il7r</i>-enriched DNT-associated lymphoid population, findings compatible with local IL-7-associated microenvironmental cues that may contribute to conditioning infiltrating T cells. Functionally, IL-7R was required for efficient CD8 upregulation after ovarian localization, and IL-7R or IL-7 deficiency shifted the endogenous ovarian DNT: CD8<sup>+</sup> T cell balance. These findings support the ovary as an immune-conditioning environment in which tissue entry is associated with CD8 coreceptor induction on peripheral DNTs, and identify IL-7R signaling as a requirement for efficient induction in this setting.</p>

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

  • Toni Martin,
  • Howard A. Young,
  • Enitome E. Bafor

摘要

The ovary is an immunologically dynamic tissue that coordinates recurrent inflammation-like remodeling while preserving local T cell tolerance, yet whether it actively instructs infiltrating lymphocyte phenotype or passively enriches pre-existing subsets has not been directly tested. To address this, we used peripheral double-negative T cells (DNTs; CD3+CD4CD8NK1.1) as a coreceptor-null system to detect tissue-imposed phenotypic change after ovarian entry. Using adoptive transfer, labeled splenic DNTs accumulated in the ovary relative to other tissue sites, and donor DNTs acquired surface CD8 expression within 4 days of ovarian localization. Dissociated ovarian cells were sufficient to drive CD8 upregulation on sorted DNTs in vitro, supporting that ovarian cellular cues can promote this response. Ovarian single-cell RNA-seq provided supportive evidence for Il7-expressing stromal subsets, and an Il7r-enriched DNT-associated lymphoid population, findings compatible with local IL-7-associated microenvironmental cues that may contribute to conditioning infiltrating T cells. Functionally, IL-7R was required for efficient CD8 upregulation after ovarian localization, and IL-7R or IL-7 deficiency shifted the endogenous ovarian DNT: CD8+ T cell balance. These findings support the ovary as an immune-conditioning environment in which tissue entry is associated with CD8 coreceptor induction on peripheral DNTs, and identify IL-7R signaling as a requirement for efficient induction in this setting.