Human Seminal Plasma Fosters CD4⁺ Regulatory T-cell Phenotype and Transforming Growth Factor-β1 Expression

Problem: Semen mediates expansion of CD4⁺ regulatory T cells (Treg) in the murine female reproductive tract. The impact of semen on Treg in humans, however, remains unclear. Method of Study: Using seminal plasma (SP) from 20 healthy donors, we investigated the impact of human semen on CD4⁺ T-cell expression of CD127 and CD49d as well as CD4⁺ CD127^low CD49d^low Treg proliferation, apoptosis, and intracellular expression of FoxP3, TGF-β1, and IL-10. Results: SP reduced CD4⁺ T-cell expression of CD127 and CD49d and increased the proportion of CD127^low CD49d^low Treg. This increase was non-proliferative, mediated in part via the conversion of CD4⁺ helper T cells into FoxP3^- but not FoxP3⁺ Treg. Additionally, SP induced an increase in intracellular expression of the immunosuppressive cytokine TGF-β1 by the FoxP3^- but not FoxP3⁺ Treg. SP had no impact on Treg intracellular expression of IL-10. Conclusion: Human seminal plasma fosters the non-proliferative increase in the proportion and immunoregulatory activity of FoxP3^- Treg.