Figure 1

Hypothesis of the setting and maintenance of immune tolerance to spermatozoa in the epididymis. It seems that various mechanisms/cells/molecules are at work in the different epididymis segments. The first segment (S1) is filled with a dense network of dendritic cells able to reach the lumen. They could thus potentially sample luminal antigens (and among them sperm antigens) to present them to local (epithelium-resident T cells) or distant (proximal lymph node-resident T cells) immunoregulatory cells. The lack of immunomodulatory molecules could explain the slight inflammation we previously described in this segment. Spermatozoa entry into the epididymal tubule induces the expression of indoleamine 2,3-dioxygenase (IDO1), which can be found as soon as the second segment (S2), and of its enzymatic products, the kynurenines. The combination of numerous dendritic cells and IDO1 expression leads to a reduction in the local inflammation observed in the initial segment. IDO1 expression reaches its maximum in the third segment (S3) leading to a strong increase in kynurenine concentrations. The later induce the differentiation of regulatory T lymphocytes which produce immunomodulatory molecules such as TGF-β1 or IL-10, ending in the suppression of effector T cells (Th17 or Th1). In the same time, the loss of dendrites on the dendritic cells suggests that at this level of the epididymis tubule they may become accessory cells in the maintenance of tolerance.