Sperm and Testicular Autoimmunity

Tung, Kenneth S. K.

doi:10.1016/b978-0-12-596920-8.50028-7

Cited by 29 publications

(21 citation statements)

References 123 publications

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“…According to prevailing dogma, the BTB formed by Sertoli cells in normal testis completely sequesters male meiotic germ cell antigens from immune recognition (2,30) and these antigens are therefore more "foreign" than "self." However, the validity of this paradigm is in dispute for the following reasons.…”

Section: Discussionmentioning

confidence: 99%

“…The postvasectomy autoimmune response has likely resulted from continuous stimulation by exposed sperm antigens coming from the inflamed epididymis. However, the magnitude and incidence of the sperm antibody response vary greatly (30% to >80%), and the onset is often late (6-9 mo) (2,3). We hypothesize that vasectomy may trigger an immunoregulatory process concomitant with an adaptive immune response to sperm antigens.…”

Section: Foxp3mentioning

confidence: 99%

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

Wheeler

Tardif

Rival

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

114

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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+ 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 functiona possible genetic trait-can influence the divergent tolerogenic versus autoimmune response to vasectomy.vasoligation | testis autoantigen | granulomatous inflammation | innate response

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Section: Discussionmentioning

confidence: 99%

Section: Foxp3mentioning

confidence: 99%

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

Wheeler

Tardif

Rival

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

114

View full text Add to dashboard Cite

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“…Autoimmune response to sperm antigens is an established fact, and is the basis for infertility in men undergoing vasectomy (Alexander 1975, Alexander & Anderson 1979, Rose & Lucas 1979, Tung & Menge 1985, Flickinger et al 1986.…”

Section: Development Of Type 1 Microcanalmentioning

confidence: 99%

Microcanalization in the epididymis to overcome ductal obstruction caused by chronic exposure to chromium – a study in the mature bonnet monkey (Macaca radiata Geoffroy)

Aruldhas¹,

Subramanian²,

Sekhar³

et al. 2004

Reproduction

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In order to apprehend the toxic effects of chromium, an occupational/environmental pollutant, on the epididymis, adult bonnet monkeys were exposed to chromium (VI) in their drinking water at concentrations of 100, 200 and 400 p.p.m. for a chronic period of 180 days. At the end of the experimental period, testicles and segments of epididymis from control and treated monkeys were subjected to light microscopic (resin-embedded semi-thin sections) and transmission electron microscopic analyses. Among the various changes undergone by the epididymal epithelium, the present paper describes the origin of two different kinds of microcanals, probably caused by ductal obstruction. The first type of microcanal, which appears to provide passage for spermatozoa to bypass the obstructed main duct, is comparable with the one already reported in carbendazimtreated efferent ductules of the rat. The second type of microcanal, which is novel, consisted of a lumen in the epithelium enclosed by four to five cells, which are either modified basal cells, principal cells or a hitherto unknown cell type. This novel type of microcanal is suggested to be a device to entrap the spermatozoa which reach the core of the epithelium and may be a mechanism to prevent extravasation of sperm so as to avoid an autoimmune response of spermatic granuloma formation. Thus, the present study has shown that chronic exposure to chromium (VI) through drinking water can produce pathological manifestations in the epididymal epithelium but the epididymis, being a versatile organ, is capable of overcoming such adverse situations through novel devices.

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“…Degeneration and exfoliation of sperm, spermatids, and spermatocytes are believed to represent a lesion mediated by a humoral antibody that has reached the lumen of the seminiferous tubules, and the macrophagic invasive lesion in the testis resembles a delayed hypersensitivity type of reaction mediated by TLBCs [15]. Recently, more experiments have given evidence of the active role of TLBCs in the pathogenesis of EAO.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the vast majority of passive transfers of EAO has been in the guinea pig system [15]. There have been only a few reports of EAO transfer in mice [3, 9, 101. In addition, transfer of EAO was induced by injection of immune serum, immune lymphoid cells, and peritoneal exudate cells including various immunocompetent cells, so that it is rather difficult to explain the complex immunologic mechanism.…”

Section: Y Feng Et Almentioning

confidence: 99%

Adoptive Transfer of Murine Autoimmune Orchitis With Sperm-Specific T Lymphoblasts

Zhang

Wang

et al. 1990

Archives of Andrology

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A protocol was successfully developed for reproducibly transferring experimental autoimmune orchitis (EAO) to naive recipient mice with sperm-specific T lymphoblasts. Cell donors were Balb/c mice immunized about 12 days earlier with homologous epididymal sperm capacitated in vitro with complete Freund's adjuvant. Draining lymph node cells were collected and subjected to a second challenge with the same sperm antigen in vitro. Sperm-specific T lymphoblasts were isolated on Percoll density gradients and propagated in the presence of interleukin-2 for 3 days and then were transferred intraperitoneally to naive recipients. As few as 3 X 106 sperm-specific T lymphoblasts were able to transfer EAO, which began on day 7 as infiltration of lymphocytes and macrophages and on days 14 to 21 developed to degenerative changes of spermatids and exfoliation of germinal epithelium. These pathologic alterations resemble a delayed type of hypersensitivity. The results show that sensitized T lymphoblasts can mediate an antigen-specific, mononuclear cell-invasive lesion in autoimmune orchitis.

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Sperm and Testicular Autoimmunity

Cited by 29 publications

References 123 publications

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

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

Microcanalization in the epididymis to overcome ductal obstruction caused by chronic exposure to chromium – a study in the mature bonnet monkey (Macaca radiata Geoffroy)

Adoptive Transfer of Murine Autoimmune Orchitis With Sperm-Specific T Lymphoblasts

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