Exosomes in human semen impair antigen-presenting cell function and decrease antigen-specific T cell responses

Abstract

Abstract Exposure to semen is the primary route of transmission for many sexually transmitted infections. Accumulating evidence suggests that components in semen directly impair leukocytes, which could compromise the protective efficacy of vaccine-induced immune responses in the mucosa. Exosomes, small microvesicles with immunomodulatory functions, are present at an average concentration of 2.2 × 1013 particles per ejaculate (n = 18). These seminal exosomes (SE) efficiently and rapidly entered peripheral and vaginal dendritic cells (DCs), whereas T cell uptake was poor. In PBMC cultures, SE impaired memory T cell function, reducing the production of TNF-alpha, IL-2 and/or IFN-gamma in response to virus-derived peptides an average of 60% for CD4+ T cells and 48% for CD8+ T cells, in a dose-responsive manner (n = 6). Reduction of cytokine production by memory CD8+ T cells was reduced to a greater extent for protein antigens as compared to peptide antigens, implying that antigen-presenting cell function was impaired by the presence of SE. Exposing only DCs, as opposed to bulk PBMCs, to SE also blocked subsequent CD8+ memory T cell activation, reducing the proportion of cells making cytokines by 22% (n = 5 donors). Expression of CD107a, a marker of cytotoxic T cell degranulation, was decreased by 42% in PBMC cultures exposed to SE and superantigen (n=4). SE also impaired vaginal T cell cytokine and degranulation responses to superantigen. Thus, SE likely inhibit antigen-specific T cell responses by impairing antigen-presenting cell function. Understanding how programmed immune responses are altered by the presence of semen is important to developing the next generation of vaccine and preventative treatments against sexually transmitted disease