ArticleProceedings of the National Academy of Sciences of the United States of America2011
Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 104 citations in OpenAlex.
- Advances in understanding the dual roles of testicular immune responses: From immune privilege to inflammation.Seminars in immunopathology · 2026Review
- Immunological dynamics of the epididymis: from experimental insights to clinical translation.Reproduction & fertility · 2026Review
- Advances in immunological research on male infertility.Frontiers in reproductive health · 2026Review
- Chronic inflammation drives epididymal tertiary lymphoid structure formation and autoimmune fertility disorders in mice.Nature communications · 2025Article
- Human efferent ductules and epididymis display unique cell lineages with motile and primary cilia.Andrology · 2025Article
- Immune Regulation in the Testis and Epididymis.Advances in experimental medicine and biology · 2025Review
- A Comprehensive Bibliometric Analysis of Orchitis Research from 1980 to 2023.Advances in experimental medicine and biology · 2025Review
- The mouse epididymal amyloid matrix is a mammalian counterpart of a bacterial biofilm.iScience · 2024Article
- A pathological joint-liver axis mediated by matrikine-activated CD4Signal transduction and targeted therapy · 2024Article
- Immune Checkpoint Inhibitors and Male Fertility: Should Fertility Preservation Options Be Considered before Treatment?Cancers · 2024Review
- Article
- Regulatory T cells play a crucial role in maintaining sperm tolerance and male fertility.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A Narrative Review Discussing Vasectomy-Related Impact upon the Status of Oxidative Stress and Inflammation Biomarkers and Semen Microbiota.Journal of clinical medicine · 2023Review
- Characterization of anti-erythrocyte and anti-platelet antibodies in hemolytic anemia and thrombocytopenia induced byFrontiers in cellular and infection microbiology · 2023Article
- Host defense functions of the epididymal amyloid matrix.Molecular human reproduction · 2022Article
- Somatic-Immune Cells Crosstalk In-The-Making of Testicular Immune Privilege.Reproductive sciences (Thousand Oaks, Calif.) · 2022Review
- Rapid divergence of a gamete recognition gene promoted macroevolution of Eutheria.Genome biology · 2022Article
- Viral tropism for the testis and sexual transmission.Frontiers in immunology · 2022Review
- Implications of regulatory T cells in non-lymphoid tissue physiology and pathophysiology.Frontiers in immunology · 2022Review
- Exposed and Sequestered Antigens in Testes and Their Protection by Regulatory T Cell-Dependent Systemic Tolerance.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Vasectomy is a well accepted global contraceptive approach frequently associated with epididymal granuloma and sperm autoantibody 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, (i) Treg normally prevents spontaneous organ-specific autoimmunity induction by persistent endogenous danger signal, and (ii) autoantigenic stimulation with sterile autoinflammation 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.