Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy.

2.50
Hdl Handle:
http://hdl.handle.net/10033/200329
Title:
Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy.
Authors:
Wheeler, Karen; Tardif, Steve; Rival, Claudia; Luu, Brian; Bui, Elise; Del Rio, Roxana; Teuscher, Cory; Sparwasser, Tim; Hardy, Daniel; Tung, Kenneth S K
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.
Affiliation:
Department of Pathology and Beirne B Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908, USA.
Citation:
Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy. 2011, 108 (18):7511-6 Proc. Natl. Acad. Sci. U.S.A.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
3-May-2011
URI:
http://hdl.handle.net/10033/200329
DOI:
10.1073/pnas.1017615108
PubMed ID:
21502500
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorWheeler, Karenen
dc.contributor.authorTardif, Steveen
dc.contributor.authorRival, Claudiaen
dc.contributor.authorLuu, Brianen
dc.contributor.authorBui, Eliseen
dc.contributor.authorDel Rio, Roxanaen
dc.contributor.authorTeuscher, Coryen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorHardy, Danielen
dc.contributor.authorTung, Kenneth S Ken
dc.date.accessioned2012-01-05T15:10:58Z-
dc.date.available2012-01-05T15:10:58Z-
dc.date.issued2011-05-03-
dc.identifier.citationRegulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy. 2011, 108 (18):7511-6 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn1091-6490-
dc.identifier.pmid21502500-
dc.identifier.doi10.1073/pnas.1017615108-
dc.identifier.urihttp://hdl.handle.net/10033/200329-
dc.description.abstractVasectomy 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.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAutoantibodiesen
dc.subject.meshAutoimmunityen
dc.subject.meshBlotting, Westernen
dc.subject.meshCell Proliferationen
dc.subject.meshElectrophoresis, Polyacrylamide Gelen
dc.subject.meshImmune Toleranceen
dc.subject.meshMaleen
dc.subject.meshMembrane Proteinsen
dc.subject.meshMiceen
dc.subject.meshMice, Mutant Strainsen
dc.subject.meshSpermatozoaen
dc.subject.meshStatistics, Nonparametricen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.subject.meshVasectomyen
dc.titleRegulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology and Beirne B Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908, USA.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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