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

Content Provider	PubMed Central
Author	Wheeler, Karen Tardif, Steve Rival, Claudia Luu, Brian Bui, Elise Rio, Roxana Del 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.
Related Links	http://dx.doi.org/10.1073/pnas.1017615108
Starting Page	7511
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	18
Volume Number	108
Language	English
Publisher	National Academy of Sciences
Publisher Date	2011-05-03
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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