Seminal vesicle fluid ameliorates autoimmune response within central nervous system.

Abstract

In 2004, it was demonstrated that changes in female reproductive tissue due to insemination result in immunological priming to paternal antigens and influence pregnancy outcome. During mating, exposure to seminal fluid elicits a tolerant state to paternal allo-antigens by expanding the regulatory T cell (Treg) pool. Notably, mating with males with surgically removed seminal vesicle glands was shown to fail to induce such effects.1 Evidence of antigen-specific Treg responses2,3,4 suggested that the expansion of the Treg pool occurs in response to seminal vesicle fluid.6 Further research has revealed differential recruitment of Tregs into different tissues, including the liver, kidney, heart, spleen, lymph nodes, mucosal tissues, blood, skin, thymus and brain, of which recruitment to the brain was the lowest.1 Owing to these effects on Treg expansion and the lower recruitment to the brain, we administered seminal vesicle fluid via an intra- cerebrospinal fluid (CSF) route in a Lewis rat model of experimental autoimmune encephalomyelitis (EAE) and investigated its effect on Treg expansion and clinical disease course. We induced EAE in Lewis rats and treated them with saline, 0.1 mg/ml chymotrypsin or seminal vesicle fluid (liquefied using chymotrypsin). Then, IFN-γ, IL-4, IL-17 and FoxP3 expression were estimated using a two-step real-time PCR method on samples from the brain, spinal cord and deep cervical lymph node (Supplementary Information). Our EAE Lewis rat model exhibited an acute monophasic disease, with clinical signs beginning on day 7 and reached the peak of the disease on day 14 post-induction. Intra-CSF injection of seminal vesicle fluid, 0.1 mg/ml chymotrypsin or saline was performed on day 7 after EAE induction. Changing trends in clinical signs in seminal vesicle fluid-treated animals were markedly different from those in the animals treated with 0.1 mg/ml chymotrypsin or saline (Figure 1a). The maximum mean clinical scores during the course of study were 1.46, 1.41 and 0.41, in saline-, 0.1 mg/ml chymotrypsin- and seminal vesicle fluid-treated animals, respectively.