Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Del Rio, Roxana
Tung, Kenneth S K
MetadataShow full item record
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.
CitationRegulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy. 2011, 108 (18):7511-6 Proc. Natl. Acad. Sci. U.S.A.
AffiliationDepartment of Pathology and Beirne B Carter Center of Immunology, University of Virginia, Charlottesville, VA 22908, USA.
The following license files are associated with this item:
- Regulatory T cells and vasectomy.
- Authors: Rival C, Wheeler K, Jeffrey S, Qiao H, Luu B, Tewalt EF, Engelhard VH, Tardif S, Hardy D, del Rio R, Teuscher C, Tung K
- Issue date: 2013 Nov
- Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis.
- Authors: Qu N, Terayama H, Naito M, Ogawa Y, Hirai S, Kitaoka M, Yi SQ, Itoh M
- Issue date: 2008 Jun
- Developmental ontogeny of autoantigens associated with localized autoimmunity in murine testis and epididymis.
- Authors: Qu N, Naito M, Terayama H, Hirai S, Li J, Ogawa Y, Kitaoka M, Itoh M
- Issue date: 2010 Dec
- Experimental autoimmune orchitis after neonatal thymectomy in the mouse.
- Authors: Taguchi O, Nishizuka Y
- Issue date: 1981 Nov
- Consequences of autoimmunity to sperm antigens in vasectomized men.
- Authors: Anderson DJ, Alexander NJ
- Issue date: 1979 Dec