Exosomes in human semen impair antigen-presenting cell function and decrease antigen-specific T cell responses (MUC7P.767)

Abstract

Abstract Exposure to semen is the primary route of transmission for many sexually transmitted infections. Mounting evidence suggests that components in semen directly influence leukocytes, which could help to explain the difficulty of inducing vaccination-based protection in the genital mucosa. Exosomes, small microvesicles with demonstrated immunomodulatory functions, are present at an average concentration of 2.2 x 1013 particles per ejaculate (n = 18 healthy semen donors). These seminal exosomes (SE) efficiently and rapidly entered peripheral and vaginal dendritic cells (DCs), whereas T cell uptake of SE was poor. SE impaired the immune responses of DCs stimulated by bacterial lipopolysaccharide, where cytokine production was reduced at both the mRNA level in the cells and the protein level in supernatants. Preliminary experiments also indicated that SE down-regulate CD80 and CD83 expression on DCs. In PBMC cultures, SE impaired memory T cell function, reducing the production of TNF-alpha and/or IFN-gamma in response to virus-derived peptides an average of 73% for CD4+ T cells and 55% for CD8+ T cells, in a dose-responsive manner (n = 4 PBMC donors). Thus, SE likely inhibit antigen-specific T cell responses by affecting the co-stimulatory capacity of antigen-presenting cells. 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.