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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy
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Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy

机译：调节性T细胞在输精管切除术中控制对精子的耐受性与自身免疫反应

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摘要

Vasectomy is a well accepted global contraceptive approach frequently associated with epididymal granuloma and sperm autoanti-body formation. To understand the long-term sequelae of vasectomy, we investigated the early immune response in vasectomized mice. Vasectomy leads to rapid epithelial cell apoptosis and necrosis, persistent inflammation, and sperm granuloma formation in the epididymis. Vasectomized B6AF1 mice did not mount autoimmune response but instead developed sperm antigen-specific tolerance, documented as resistance to immunization-induced experimental autoimmune orchitis (EAO) but not experimental autoimmune encephalomyelitis. Strikingly, tolerance switches over to pathologic autoimmune state following concomitant CD4~+CD25~+Foxp3~+ regulatory T cell (Treg) depletion: unilaterally vasectomized mice produce dominant autoantibodies to an orchitogenic antigen (zonadhesin), and develop CD4 T-cell- and antibody-dependent bilateral autoimmune orchitis. Therefore, (/) Treg normally prevents spontaneous organ-specific autoimmunity induction by persistent endogenous danger signal, and (/;) autoantigenic stimulation with sterile autoin-flammation can lead to tolerance. Finally, postvasectomy tolerance occurs in B6AF1, C57BL/6, and A/J strains. However, C57BL/6 mice resisted EAO after 60% Treg depletion, but developed EAO after 97% Treg reduction. Therefore, variance in intrinsic Treg function— a possible genetic trait—can influence the divergent tolerogenic versus autoimmune response to vasectomy.
机译：输精管切除术是一种广为接受的全球避孕方法，通常与附睾肉芽肿和精子自身抗体形成有关。为了了解输精管切除术的长期后遗症，我们研究了在输精管切开术的小鼠中的早期免疫反应。输精管结扎术会导致快速的上皮细胞凋亡和坏死，持续的炎症以及附睾中精子肉芽肿的形成。接受输精管切除术的B6AF1小鼠未发生自身免疫反应，但发展出了精子抗原特异性耐受性，据记载对免疫诱导的实验性自身免疫性睾丸炎（EAO）具有抵抗力，但对实验性自身免疫性脑脊髓炎没有抵抗力。令人惊讶的是，在伴随CD4〜+ CD25〜+ Foxp3〜+调节性T细胞（Treg）耗竭后，耐受性转变为病理性自身免疫状态：单侧输精管切除的小鼠产生针对睾丸抗原（zonadhesin）的优势自身抗体，并发育CD4 T细胞和抗体依赖性双侧自身免疫性睾丸炎。因此，（/）Treg通常通过持续的内源性危险信号阻止自发的器官特异性自身免疫诱导，并且（/;）无菌自体炎症引起的自体抗原刺激可导致耐受。最后，在B6AF1，C57BL / 6和A / J菌株中发生输精管切除术后的耐受性。但是，C57BL / 6小鼠在60％的Treg耗竭后抵抗EAO，但在97％的Treg降低后发展为EAO。因此，内在的Treg功能（一种可能的遗传特征）的差异会影响对输精管切除术的耐受性和自身免疫反应的差异。

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    Karen Wheeler; Steve Tardif; Claudia Rival; Brian Luu; Elise Bui; Roxana del Rio; Cory Teuscher; Tim Sparwasser; Daniel Hardy; Kenneth S. K. Tung;

  • 作者单位

    Department of Pathology and Beirne B. Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908;

    Department of Cell Biology andBiochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430;

    Department of Pathology and Beirne B. Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908;

    Department of Pathology and Beirne B. Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908;

    Department of Pathology and Beirne B. Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908;

    Department of Medicine, University of Vermont, Burlington, VT 05405;

    Department of Medicine, University of Vermont, Burlington, VT 05405;

    lnstitute of Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, 30625 Hannover, Germany;

    Department of Cell Biology andBiochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430;

    Department of Pathology and Beirne B. Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    vasoligation; testis autoantigen; granulomataus inflammation; innate; response;

    机译：血管沉着;睾丸自身抗原;肉芽肿性炎症;先天性;反应;

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