Skip to main content
SpringerLink
Log in

Testicular Autoimmunity by Alteration of the Immune System in Experimental Animals

  • Chapter
  • First Online:
Testicular Autoimmunity

  • 376 Accesses

Abstract

Experimental autoimmune orchitis (EAO) is not confined to animals that received artificial exposure to TGC autoantigens experimentally but occurs spontaneously in some animals with abnormal condition of immune system.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Chan AY, Anderson MS. Central tolerance to self revealed by the autoimmune regulator. Ann N Y Acad Sci. 2015;1356:80–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DA. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007;450:566–9.

    Article  CAS  PubMed  Google Scholar 

  • Del Rio R, Sun Y, Alard P, Tung KS, Teuscher C. H2 control of natural T regulatory cell frequency in the lymph node correlates with susceptibility to day 3 thymectomy-induced autoimmune disease. J Immunol. 2011;186:382–9.

    Article  CAS  PubMed  Google Scholar 

  • Deng T, Chen Q, Han D. The role of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites. Front Biosci. 2016;21:316–27.

    Article  Google Scholar 

  • Dyson PJ, Knight AM, Fairchild S, Simpson E, Tomonair K. Genes encoding ligands for deletion of V beta11 T cells cosegregate with mammary tumor virus genomes. Nature. 1991;349:431–532.

    Article  Google Scholar 

  • Eldershaw SA, Sansom DM, Narendran P. Expression and function of the autoimmune regulator (Aire) gene in non-thymic tissue. Clin Exp Immunol. 2011;163:296–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Filaci G, Fenoglio D, Indiveri F. CD8+ T regulatory/suppressor cells and their relationships with autoreactivity and autoimmunity. Autoimmunity. 2011;44:51–7.

    Article  CAS  PubMed  Google Scholar 

  • Grigorev VV, Ogurtsov RP, Zubzhitsi IN. Immunomorphologic changes in the testes upon exposure to a microwave electromagnetic field. Arkh Anat Gistol Embriol. 1981;80:69–75.

    CAS  Google Scholar 

  • Hammer RE, Marika SD, Richardson JA, Tang JYP, Taurig JD. Transgenic rats expressing HLA-B27 and human b2 microglobulin with spontaneous inflammatory disease in multiple organ systems: an animal model of HLA-B27-associated disease. Cell. 1990;63:1099–112.

    Article  CAS  PubMed  Google Scholar 

  • Hattori M, Brandon MR. Thymus and the endocrine system: ovarian dysgenesis in neonatally thymectomized rats. J Endocrinol. 1979;83:101–11.

    Article  CAS  PubMed  Google Scholar 

  • Hedger MP. Toll-like receptors and signaling in spermatogenesis and testicular responses to inflammation-a perspective. J Reprod Immunol. 2011a;88:130–41.

    Article  CAS  PubMed  Google Scholar 

  • Hedger MP. Immunophysiology and pathology of inflammation in the testis and epididymis. J Androl. 2011b;32:625–40.

    Article  CAS  PubMed  Google Scholar 

  • Hiramine C, Hojo K, Matsumoto H, Koseto M, Itoh M. Differential effect of cyclosporine in vivo on the distribution of T cell subsets in the thymus, spleen, and lymph nodes. Transplantation. 1989a;47:499–503.

    Google Scholar 

  • Hiramine C, Hojo K, Koseto M, Itoh M. The effect of cyclosporine on thymic epithelial cells-an immunohistochemical study. Thymus. 1989b;14:213–21.

    CAS  PubMed  Google Scholar 

  • Hou WG, Zhao J, Li Z, Li W, Li T, Xiong LZ, Zhang YQ. Effects of electromagnetic pulse irradiation on the mouse blood-testicle barrier. Urology. 2012;80(225):e1–6.

    Google Scholar 

  • Hubert FX, Kinkel SA, Crewther PE, Cannon PZ, Webster KE, Link M, Uibo R, O’Bryan MK, Meager A, Forehan SP, Smyth GK, Mittaz L, Antonarakis SE, Peterson P, Health WR, Scott HS. Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype. J Immunol. 2009;182:3902–18.

    Article  CAS  PubMed  Google Scholar 

  • Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otuka F, Sakaguchi S. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol. 1999;162:5317–26.

    CAS  PubMed  Google Scholar 

  • Jones LA, Chin T, Merriam GR, Nelson LM, Kruisbeck AM. Failure of clonal deletion in neonatally thymectomized mice: tolerance is preserved through clonal anergy. J Exp Med. 1990;139:1277–85.

    Article  Google Scholar 

  • Kisand K, Peterson P. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: known and novel aspects of the syndrome. Ann N Y Acad Sci. 2011;1246:77–91.

    Article  CAS  PubMed  Google Scholar 

  • Kojima A, Spencer CA. Genetic susceptibility to testicular autoimmunity: comparison between postthymectomy and postvasectomy models in mice. Biol Reprod. 1983;29:195–205.

    Article  CAS  PubMed  Google Scholar 

  • Kojima A, Prehn RT. Genetic susceptibility to post-thymectomy autoimmune diseases in mice. Immunogenetics. 1981;14:15–27.

    Article  CAS  PubMed  Google Scholar 

  • Lipscomb HL, Gardner PJ, Sharp G. The effect of neonatal thymectomy on the induction of autoimmune orchitis in rats. J Reprod Immunol. 1979;1:209–17.

    Article  CAS  PubMed  Google Scholar 

  • Luo Y, Wang X, Chen Y, Xu S, Ding G, Shi C. Effects of electromagnetic radiation on morphology and TGF-beta3 expression in mouse testicular tissue. Toxicology. 2013;310:8–14.

    Article  CAS  PubMed  Google Scholar 

  • Lu Q, Gore M, Zhang Q, Camenisch T, Boast S, Casagrandra F, Lai C, Skinner MK, Klein R, Matsushima GK, Earp HS, Goff SP, Lemke G. Tyro-3 family receptors are essential of mammalian spermatogenesis. Nature. 1999;398:723–8.

    Article  CAS  PubMed  Google Scholar 

  • Lu Q, Lemke G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science. 2001;293:306–11.

    Article  CAS  PubMed  Google Scholar 

  • Miller JF. Analysis of the thymus influence in leukaemogenesis. Nature. 1961;191:248–9.

    Article  CAS  PubMed  Google Scholar 

  • Morimoto T, Nishigaki-Maki K, Ohno K, Ikeda H, Takeuchi M, Ueda T, Takahashi T, Taguchi O. Transplantation of xenogeneic embryonic thymus to athymic nude mice induces acquisition of distorted immunity. Transplant Proc. 2000;32:956–7.

    Article  CAS  PubMed  Google Scholar 

  • Nishigaki-Maki K, Takahashi T, Ohno K, Morimoto T, Ikeda H, Takeuchi M, Ueda M, Taguchi O. Autoimmune diseases developed in athymic nude mice grafted with embryonic thymus of xenogeneic origin. Eur J Immunol. 1999;29:3350–9.

    Article  CAS  PubMed  Google Scholar 

  • Nishizuka Y, Sakakura T. Thymus and reproduction: sex linked dysgenesis of the gonad after neonatal thymectomy. Science. 1969;166:753–5.

    Article  CAS  PubMed  Google Scholar 

  • Nishizuka Y. A novel experimental system of organ-localized autoimmune disease in the mouse. Acta Pathol Jpn. 1982;32:211–22.

    PubMed  Google Scholar 

  • Ohno K, Takahashi T, Maki K, Ueda M, Taguchi O. Successful transfer of localized autoimmunity with positively selected CD4+ cells to scid mice lacking functional B cells. Autoimmunity. 1999;29:103–10.

    Article  CAS  PubMed  Google Scholar 

  • Pitkanen J, Peterson P. Autoimmune regulator: from loss of function to autoimmunity. Genes Immun. 2003;4:12–21.

    Article  CAS  PubMed  Google Scholar 

  • Radhakrishnan K, Bhagya KP, Kumar AT, Devi AN, Sengottaiyan J, Kumar PG. Autoimmune regulator (Aire) is expressed in spermatogenic cells, and it altered the expression of several nucleic-acid-biding and cytoskeletal proteins in germ cell 1 spermatogonial (GC1-spg) cells. Mol Cell Proteomics. 2016;15:2686–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramonda R, Foresta C, Ortolan A, Bertoldo A, Oliviero F, Lorenzin M, Pizzol D, Punzi L, Garolla A. Influence of tumor necrosis factor alpha inhibitors on testicular function and semen in spondyloarthritis patients. Fertil Steril. 2014;101:359–65.

    Article  CAS  PubMed  Google Scholar 

  • Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kampe O, Eskelin P, Pelto-Huikko M, Peltonen L. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet. 2002;11:397–409.

    Article  CAS  PubMed  Google Scholar 

  • Ruan QG, Wang CY, Shi JD, She JX. Expression and alternative splicing of the mouse autoimmune regulator gene (Aire). J Autoimmun. 1999;13:307–13.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T. Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cell in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med. 1985;161:72–87.

    Google Scholar 

  • Sakaguchi S, Sakaguchi N. Thymus and autoimmunity. Transplantation of the thymus from cyclosporine A-treated mice causes organ-specific autoimmune disease in athymic nude mice. J Exp Med. 1988;167:1479–85.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S, Sakaguchi N. Organ-specific autoimmune disease induced by elimination of T cell subsets. V. Neonatal administration of cyclosporine A causes autoimmune disease. J Immunol. 1989;142:471–80.

    Google Scholar 

  • Sakaguchi S, Sakaguchi N. Thymus and autoimmunity: Capacity of the normal thymus to produce self-reactive T cells and conditions required for their induction of autoimmune disease. J Exp Med. 1990;172:537–45.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi N, Sakaguchi S. Causes and mechanism of autoimmune disease: cyclosporine A as a probe for the investigation. J Invest Dermatol. 1992;98:79S–6S.

    Article  Google Scholar 

  • Sakaguchi N, Miyai K, Sakaguchi S. Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells. J Immunol. 1994a;152:2586–95.

    CAS  PubMed  Google Scholar 

  • Sakaguchi S, Ermak TH, Toda M, Berg LJ, Ho W, de St Groth BF, Peterson PA, Sakaguchi N, Davis MM. Induciton of autoimmune disease in mice by germline alteration of the T cell receptor gene expression. J Immunol. 1994b;152:1471–84.

    CAS  PubMed  Google Scholar 

  • Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). J Immunol. 1995;155:1151–64.

    CAS  PubMed  Google Scholar 

  • Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL, Earp HS, Matsushima GK. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature. 2001;411:207–11.

    Article  CAS  PubMed  Google Scholar 

  • Schaller CE, Wang CL, Beck-Engeser G, Goss L, Scott HS, Anderson MS, Wabl M. Expression of Aire and the early wave of apoptosis in spermatogenesis. J Immunol. 2008;180:1338–43.

    Article  CAS  PubMed  Google Scholar 

  • Smith H, Chen IM, Kubo R, Tung KSK. Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus. Science. 1989;245:749–52.

    Article  CAS  PubMed  Google Scholar 

  • Smith H, Sakamoto Y, Kasai K, Tung KSK. Effector and regulatory cells in autoimmune oophoritis elicited by neonatal thymectomy. J Immunol. 1991;147:2928–33.

    CAS  PubMed  Google Scholar 

  • Smith H, Lou YH, Lacy P, Tung KSK. Tolerance mechanism in ovarian and gastric autoimmune disease. J Immunol. 1992;149:2212–8.

    CAS  PubMed  Google Scholar 

  • Smith TR, Kumar V. Revival of CD8+ Treg-mediated suppression. Trends Immunol. 2008;29:337–42.

    Article  CAS  PubMed  Google Scholar 

  • Son Y, Heo K, Bae MJ, Lee CG, Cho WS, Kim SD, Yang K, Shin IS, Lee MY, Kim JS. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice. Radiat Prot Dosim. 2015;167:316–20.

    Article  CAS  Google Scholar 

  • Sugihara S, Izumi Y, Yoshioka T, Yagi H, Tsujimura T, Tarutani O, Kohno Y, Murakami S, Hamaoka T, Fujiwara H. Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. I. Requirement of Lyt-1 dull L3T4 bright normal T cells for the induction of thyroiditis. J Immunol. 1988;141:105–13.

    Google Scholar 

  • Sun B, Qi N, Shang T, Wu H, Deng T, Han D. Seroli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and Mer receptors. Endocrinology. 2010;151:2886–97.

    Article  CAS  PubMed  Google Scholar 

  • Taguchi O, Nishizuka Y, Sakakura T, Kojima A. Autoimmune oophoritis in thymectomized mice: detection of circulating antibodies against oocytes. Clin Exp Immunol. 1980;40:540–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taguchi O, Nishizuka Y. Experimental autoimmune orchitis after neonatal thymectomy in the mouse. Clin Exp Immunol. 1981;46:425–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taguchi O, Takahashi T, Seto M, Namikawa R, Matsuyama M, Nishizuka Y. Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft. J Exp Med. 1986;164:60–71.

    Article  CAS  PubMed  Google Scholar 

  • Taguchi O, Nishizuka Y. Self-tolerance and localized autoimmunity: mouse models of autoimmune disease that suggest that tissue specific suppressor T cells are involved in tolerance. J Exp Med. 1987;165:146–56.

    Article  CAS  PubMed  Google Scholar 

  • Taguchi O, Takahashi T, Nishizuka Y. Self-tolerance and localized autoimmunity. Curr Opin Immunol. 1990;2:576–81.

    Article  CAS  Google Scholar 

  • Taguchi O, Kotani K, Ikeda H, Kezuka T, Takeuchi M, Takahashi T. Tissue-specific suppressor T cells involved in self-tolerance are activated extrathymically by self-antigens. Immunology. 1994;82:365–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taguchi O, Takahashi T. Administration of anti-interleukin-2 receptor antibody in vivo induced localized autoimmune disease. Eur J Immunol. 1996;26:1608–12.

    Google Scholar 

  • Takahashi K, Nagahori K, Qu N, Kuramasu M, Hayashi S, Hirai S, Hatayama N, Miyaso H, Ogawa Y, Itoh M. Effect of Goshajinkigan on the recovery of spermatogenesis after irradiation treatment in mice. 2017 (in preparation).

    Google Scholar 

  • Tang XL, Smith TR, Kumar V. Specific control of immunity by regulatory CD8 T cells. Cell Mol Immunol. 2005;2:11–9.

    CAS  PubMed  Google Scholar 

  • Taniguchi RT, Anderson MS. The role of Aire in clonal selection. Immunol Cell Biol. 2011;89:40–4.

    Article  CAS  PubMed  Google Scholar 

  • Taurog JD, Rival C, van Duivenvoorde LM, Satumira N, Dorris ML, Sun M, Shelton JM, Richardson JA, Hamra FK, Hammer RE, Tung KSK. Autoimmune epididymoorchitis is essential to the pathogenesis of male-specific spondylarthritis in HLA-B27-transgenic rats. Arthritis Rheum. 2012;64:2518–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Terayama H, Yoshimoto T, Hirai S, Naito M, Qu N, Hatayama N, Hayashi S, Mitobe K, Furusawa J, Mizoguchi I, Kezuka T, Goto H, Suyama K, Sakabe K, Itoh M. Contribution of IL-12/IL-35 common subunit p35 to maintaining testicular immune privilege. PLoS One. 2014;9(e):96120.

    Article  Google Scholar 

  • Tung KS, Smith S, Teuscher C, Cook C, Anderson RE. Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology. Am J Pathol. 1987a;126:293–302.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tung KS, Smith S, Matzner P, Kasai K, Oliver J, Feuchter F, Anderson RE. Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Autoantibodies. Am J Pathol. 1987b;126:303–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tung KS, Teuscher C. Mechanisms of autoimmune disease in the testis and ovary. Hum Reprod Update. 1995;1:35–50.

    Article  CAS  PubMed  Google Scholar 

  • Villasenor J, Benoist C, Mathis D. AIRE and APECED: molecular insights into an autoimmune disease. Immunol Rev. 2005;204:156–64.

    Article  CAS  PubMed  Google Scholar 

  • Villiger PM, Caliezi G, Cottin V, Forger F, Senn A, Ostensen M. Effects of TNF antagonists on sperm characteristics in patients with spondyloarthritis. Ann Rheum Dis. 2010;69:1842–4.

    Article  CAS  PubMed  Google Scholar 

  • Vojtiskova M, Pokorna Z. Prevention of experimental allergic aspermatogenesis by thymectomy in adult mice. Lancet. 1964;1:644–5.

    Article  CAS  PubMed  Google Scholar 

  • Wang XW, Ding GR, Shi CH, Zeng LH, Liu JY, Li J, Zhao T, Chen YB, Guo GZ. Mechanisms involved in the blood-testis barrier increased permeability induced by EMP. Toxicology. 2010;276:58–63.

    Article  CAS  PubMed  Google Scholar 

  • Woodland DL, Happ MP, Gollob KJ, Palmer E. An endogenous retrovirus mediating deletion of beta T cells? Nature. 1991;349:529–30.

    Article  CAS  PubMed  Google Scholar 

  • Xiong W, Chen Y, Wang H, Wang H, Wu H, Lu Q, Han D. Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction. 2008;135:77–87.

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Li N, Chen Q, Yan K, Liu Z, Zhang X, Liu P, Chen Y, Han D. Breakdown of immune homeostasis in the testis of mice lacking Tyro3, Axl and Mer receptor tyrosine kinases. Immunol Cell Biol. 2013;91:416–26.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, Tokyo Medical University, Shinjyuku-ku, Tokyo, Japan

    Masahiro Itoh

Authors
  1. Masahiro Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Japan

About this chapter

Cite this chapter

Itoh, M. (2017). Testicular Autoimmunity by Alteration of the Immune System in Experimental Animals. In: Testicular Autoimmunity. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54460-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54460-9_7

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54459-3

  • Online ISBN: 978-4-431-54460-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation