| Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy. | |
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MedLine Citation:
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PMID: 21502500 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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 |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-04-18 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-04 Completed Date: 2011-07-15 Revised Date: 2011-11-03 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 7511-6 Citation Subset: IM |
Affiliation:
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Department of Pathology and Beirne B Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoantibodies / immunology Autoimmunity / immunology* Blotting, Western Cell Proliferation Electrophoresis, Polyacrylamide Gel Immune Tolerance / immunology* Male Membrane Proteins / immunology Mice Mice, Mutant Strains Spermatozoa / immunology* Statistics, Nonparametric T-Lymphocytes, Regulatory / immunology* Vasectomy* |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI 41236/AI/NIAID NIH HHS; R01 AI 51420/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/Membrane Proteins; 0/zonadhesin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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