Fijak Monika, Meinhardt Andreas
Department of Anatomy and Cell Biology, Justus-Liebig-University of Giessen, Giessen, Germany.
Immunol Rev. 2006 Oct;213:66-81. doi: 10.1111/j.1600-065X.2006.00438.x.
The production, differentiation, and presence of male gametes represent inimitable challenges to the immune system, as they are unique to the body and appear long after the maturation of the immune system and formation of systemic self-tolerance. Known to protect germ cells and foreign tissue grafts from autoimmune attack, the 'immune privilege' of the testis was originally, and somewhat simplistically, attributed to the existence of the blood-testis barrier. Recent research has shown a previously unknown level of complexity with a multitude of factors, both physical and immunological, necessary for the establishment and maintenance of the immunotolerance in the testis. Besides the blood-testis barrier and a diminished capability of the large testicular resident macrophage population to mount an inflammatory response, it is the constitutive expression of anti-inflammatory cytokines in the testis by immune and particularly somatic cells, that represents an essential element for local immunosuppression. The role of androgens in testicular immune regulation has long been underestimated; yet, accumulating evidence now shows that they orchestrate the inhibition of proinflammatory cytokine expression and shift cytokine balance toward a tolerogenic environment. Furthermore, the role of the testicular dendritic cells in suppressing antigen-specific immunity and T-lymphocyte activation is discussed. Finally, the active role mast cells play in the induction and amplification of immune responses, both in infertile humans and in experimental models, highlights the importance of preventing mast cell activation to maintain the immune-privileged status of the testis.
雄性配子的产生、分化和存在对免疫系统构成了独特的挑战，因为它们是机体所特有的，且在免疫系统成熟和全身自身耐受性形成很久之后才出现。睾丸的“免疫豁免权”最初被简单地归因于血睾屏障的存在，已知它能保护生殖细胞和异体组织移植免受自身免疫攻击。最近的研究表明，睾丸免疫耐受的建立和维持涉及众多物理和免疫因素，其复杂性远超此前认知。除了血睾屏障以及睾丸中大量驻留巨噬细胞引发炎症反应的能力减弱外，睾丸中免疫细胞尤其是体细胞组成性表达抗炎细胞因子，是局部免疫抑制的关键要素。雄激素在睾丸免疫调节中的作用长期以来被低估；然而，越来越多的证据表明，它们能协调抑制促炎细胞因子的表达，并使细胞因子平衡转向致耐受性环境。此外，还讨论了睾丸树突状细胞在抑制抗原特异性免疫和T淋巴细胞激活中的作用。最后，肥大细胞在不育男性和实验模型的免疫反应诱导和放大中所起的积极作用，凸显了防止肥大细胞激活以维持睾丸免疫豁免状态的重要性。
