Immune privilege of the testis: Meaning, mechanisms, and manifestations

Infection, Immune Homeostasis and Immune Privilege

Volumn , Issue , 2012, Pages 31-52

  Hedger, Mark Peter ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

Autoimmune orchitis; Blood testis barrier; Hypogonadism; Infertility; Leydig cell; Sertoli cell; Sperm antibodies; Spermatogenesis; Steroidogenesis; Testicular macrophages

Indexed keywords

EID: 85000789906     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-0348-0445-5_2     Document Type: Chapter

References (158)

1. Aitken RJ, Baker MA (2008) The role of proteomics in understanding sperm cell biology. Int J Androl 31:295-302
2. Alexander NJ, Tung KS (1977) Immunological and morphological effects of vasectomy in the rabbit. Anat Rec 188:339-350
3. Anton F, Morales C, Aguilar R, Bellido C, Aguilar E, Gaytan F (1998) A comparative study of mast cells and eosinophil leukocytes in the mammalian testis. Zentralbl Veterinarmed A 45:209-218
4. Ariyaratne HB, Mendis-Handagama SM (2000) Changes in the testis interstitium of Sprague Dawley rats from birth to sexual maturity. Biol Reprod 62:680-690
5. Ashour HM, Niederkorn JY (2006) gd T cells promote anterior chamber-associated immune deviation and immune privilege through their production of IL-10. J Immunol 177:8331-8337
6. Baker HW (1998) Reproductive effects of nontesticular illness. Endocrinol Metab Clin North Am 27:831-850
7. Baker HW, Clarke GN, Hudson B, McBain JC, McGowan MP, Pepperell RJ (1983) Treatment of sperm autoimmunity in men. Clin Reprod Fertil 2:55-71
8. Baker HW, Clarke GN, McGowan MP, Koh SH, Cauchi MN (1985) Increased frequency of autoantibodies in men with sperm antibodies. Fertil Steril 43:438-441
9. Barker CF, Billingham RE (1977) Immunologically privileged sites. Adv Immunol 25:1-54
10. Barten EJ, Newling DW (1996) Transplantation of the testis; from the past to the present. Int J Androl 19:205-211
11. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC (1995) A role for CD95 ligand in preventing graft rejection. Nature 377:630-632
12. Bhushan S, Tchatalbachev S, Klug J, Fijak M, Pineau C, Chakraborty T, Meinhardt A (2008) Uropathogenic Escherichia coli block MyD88-dependent and activate MyD88-independent signaling pathways in rat testicular cells. J Immunol 180:5537-5547
13. Bobzien B, Yasunami Y, Majercik M, Lacy PE, Davie JM (1983) Intratesticular transplants of islet xenografts (rat to mouse). Diabetes 32:213-216
14. Bryniarski K, Szczepanik M, Maresz K, Ptak M, Ptak W (2004) Subpopulations of mouse testicular macrophages and their immunoregulatory function. Am J Reprod Immunol 52:27-35
15. Cameron DF, Whittington K, Schultz RE, Selawry HP (1990) Successful islet/abdominal testis transplantation does not require Leydig cells. Transplantation 50:649-653
16. Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC (2006) CNS immune privilege: hiding in plain sight. Immunol Rev 213:48-65
17. Chalmel F, Rolland AD, Niederhauser-Wiederkehr C, Chung SS, Demougin P, Gattiker A, Moore J, Patard JJ, Wolgemuth DJ, Jegou B, Primig M (2007) The conserved transcriptome in human and rodent male gametogenesis. Proc Natl Acad Sci USA 104:8346-8351
18. Clarke GN, Bourne H, Baker HW (1997) Intracytoplasmic sperm injection for treating infertility associated with sperm autoimmunity. Fertil Steril 68:112-117
19. Clifton VL, Husband AJ, Kay DJ (1992) Local immunity in the male reproductive tract. Immunol Cell Biol 70:301-307
20. Com E, Bourgeon F, Evrard B, Ganz T, Colleu D, Jégou B, Pineau C (2003) Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans. Biol Reprod 68:95-104
21. Czerkinsky C, Anjuere F, McGhee JR, George-Chandy A, Holmgren J, Kieny MP, Fujiyashi K, Mestecky JF, Pierrefite-Carle V, Rask C, Sun JB (1999) Mucosal immunity and tolerance:relevance to vaccine development. Immunol Rev 170:197-222
22. Dai Z, Nasr IW, Reel M, Deng S, Diggs L, Larsen CP, Rothstein DM, Lakkis FG (2005) Impaired recall of CD8 memory T cells in immunologically privileged tissue. J Immunol 174:1165-1170
23. Dal Secco V, Riccioli A, Padula F, Ziparo E, Filippini A (2008) Mouse Sertoli cells display phenotypical and functional traits of antigen-presenting cells in response to interferon gamma. Biol Reprod 78:234-242
24. De Cesaris P, Filippini A, Cervelli C, Riccioli A, Muci S, Starace G, Stefanini M, Ziparo E (1992) Immunosuppressive molecules produced by Sertoli cells cultured in vitro: biological effects on lymphocytes. Biochem Biophys Res Commun 186:1639-1646
25. Ditzian-Kadanoff R (1999) Testicular-associated immune deviation and prevention of adjuvantinduced arthritis by three tolerization methods. Scand J Immunol 50:150-158
26. Dobrinski I (2005) Germ cell transplantation and testis tissue xenografting in domestic animals. Anim Reprod Sci 89:137-145
27. Dong Q, Hawker F, McWilliam D, Bangah M, Burger H, Handelsman DJ (1992) Circulating immunoreactive inhibin and testosterone levels in men with critical illness. Clin Endocrinol 36:399-404
28. Duckett RJ, Hedger MP, McLachlan RI, Wreford NG (1997a) The effects of gonadotropinreleasing hormone immunization and recombinant follicle-stimulating hormone on the Leydig cell and macrophage populations of the adult rat testis. J Androl 18:417-423
29. Duckett RJ, Wreford NG, Meachem SJ, McLachlan RI, Hedger MP (1997b) Effect of chorionic gonadotropin and flutamide on Leydig cell and macrophage populations in the testosteroneestradiol- implanted adult rat. J Androl 18:656-662
30. Dym M, Fawcett DW (1970) The blood-testis barrier in the rat and the physiological compartmentation of the seminiferous epithelium. Biol Reprod 3:308-326
31. Dym M, Romrell LJ (1975) Intraepithelial lymphocytes in the male reproductive tract of rats and rhesus monkeys. J Reprod Fertil 42:1-7
32. el-Demiry MI, Hargreave TB, Busuttil A, Elton R, James K, Chisholm GD (1987) Immunocompetent cells in human testis in health and disease. Fertil Steril 48:470-479
33. Ergün S, Stingl J, Holstein AF (1994) Segmental angioarchitecture of the testicular lobule in man. Andrologia 26:143-150
34. Fallarino F, Luca G, Calvitti M, Mancuso F, Nastruzzi C, Fioretti MC, Grohmann U, Becchetti E, Burgevin A, Kratzer R, van Endert P, Boon L, Puccetti P, Calafiore R (2009) Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone. J Exp Med 206:2511-2526
35. Fawcett DW, Neaves WB, Flores MN (1973) Comparative observations on intertubular lymphatics and the organization of the interstitial tissue of the mammalian testis. Biol Reprod 9:500-532
36. Ferguson J, Scothorne RJ (1977) Extended survival of pancreatic islet allografts in the testis of guinea-pigs. J Anat 124:1-8
37. Fijak M, Iosub R, Schneider E, Linder M, Respondek K, Klug J, Meinhardt A (2005) Identification of immunodominant autoantigens in rat autoimmune orchitis. J Pathol 207:127-138
38. Fijak M, Schneider E, Klug J, Bhushan S, Hackstein H, Schuler G, Wygrecka M, Gromoll J, Meinhardt A (2011) Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: evidence for a direct role of testosterone on regulatory T cell expansion. J Immunol 186:5162-5172
39. Flickinger CJ, Herr JC, Howards SS, Sisak JR, Gleavy JM, Fusia TJ, Vailes LD, Handley HH (1990) Early testicular changes after vasectomy and vasovasostomy in Lewis rats. Anat Rec 227:37-46
40. Foulds LM, Boysen RI, Crane M, Yang Y, Muir JA, Smith AI, de Kretser DM, Hearn MT, Hedger MP (2008) Molecular identification of lyso-glycerophosphocholines as endogenous immunosuppressives in bovine and rat gonadal fluids. Biol Reprod 79:525-536
41. Gaytan F, Bellido C, Romero JL, Morales C, Reymundo C, Aguilar E (1994) Decreased number and size and the defective function of testicular macrophages in long-term hypophysectomized rats are reversed by treatment with human gonadotrophins. J Endocrinol 140:399-407
42. Gaytan F, Bellido C, Morales C, Garcia M, van Rooijen N, Aguilar E (1996) In vivo manipulation (depletion versus activation) of testicular macrophages: central and local effects. J Endocrinol 150:57-65
43. Ghabriel MN, Lu JJ, Hermanis G, Zhu C, Setchell BP (2002) Expression of a blood-brain barrierspecific antigen in the reproductive tract of the male rat. Reproduction 123:389-397
44. Goldacre MJ, Wotton CJ, Seagroatt V, Yeates D (2007) Immune-related disease before and after vasectomy: an epidemiological database study. Hum Reprod 22:1273-1278
45. Grossman CJ (1985) Interactions between the gonadal steroids and the immune system. Science 227:257-261
46. Haas GG Jr, D'Cruz OJ, De Bault LE (1988) Distribution of human leukocyte antigen-ABC and -D/DR antigens in the unfixed human testis. Am J Reprod Immunol Microbiol 18:47-51
47. Hardy MP, Zirkin BR, Ewing LL (1989) Kinetic studies on the development of the adult population of Leydig cells in testes of the pubertal rat. Endocrinology 124:762-770
48. Head JR, Billingham RE (1985a) Immune privilege in the testis. II. Evaluation of potential local factors. Transplantation 40:269-275
49. Head JR, Billingham RE (1985b) Immunologically privileged sites in transplantation immunology and oncology. Perspect Biol Med 29:115-131
50. Head JR, Neaves WB, Billingham RE (1983a) Immune privilege in the testis. I. Basic parameters of allograft survival. Transplantation 36:423-431
51. Head JR, Neaves WB, Billingham RE (1983b) Reconsideration of the lymphatic drainage of the rat testis. Transplantation 35:91-95
52. Hedger MP (2002) Macrophages and the immune responsiveness of the testis. J Reprod Immunol 57:19-34
53. Hedger MP (2007) Immunologically privileged environments. In: Halberstadt CR, Emerich DF (eds) Cellular transplantation from laboratory to clinic. Elsevier, Amsterdam, pp 567-590
54. Hedger MP (2011) Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation - a perspective. J Reprod Immunol 88:130-141
55. Hedger MP, Hales DB (2006) Immunophysiology of the male reproductive tract. In: Neill JD (ed) Knobil and Neill's physiology of reproduction. Elsevier, Amsterdam, pp 1195-1286
56. Hedger MP, Hettiarachchi S (1994) Measurement of immunoglobulin G levels in adult rat testicular interstitial fluid and serum. J Androl 15:583-590
57. Hedger MP, Meinhardt A (2000) Local regulation of T cell numbers and lymphocyte-inhibiting activity in the interstitial tissue of the adult rat testis. J Reprod Immunol 48:69-80
58. Hedger MP, Wang J, Lan HY, Atkins RC, Wreford NG (1998) Immunoregulatory activity in adult rat testicular interstitial fluid: relationship with intratesticular CD8+ lymphocytes following treatment with ethane dimethane sulfonate and testosterone implants. Biol Reprod 58:935-942
59. Herrid M, Vignarajan S, Davey R, Dobrinski I, Hill JR (2006) Successful transplantation of bovine testicular cells to heterologous recipients. Reproduction 132:617-624
60. 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, Heath WR, Scott HS (2009) Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype. J Immunol 182:3902-3918
61. Hudson MM, Frankel LS, Mullins J, Swanson DA (1985) Diagnostic value of surgical testicular biopsy after therapy for acute lymphocytic leukemia. J Pediatr 107:50-53
62. Hutson JC (1992) Development of cytoplasmic digitations between Leydig cells and testicular macrophages of the rat. Cell Tissue Res 267:385-389
63. Itoh M, De Rooij DG, Jansen A, Drexhage HA (1995) Phenotypical heterogeneity of testicular macrophages/dendritic cells in normal adult mice: an immunohistochemical study. J Reprod Immunol 28:217-232
64. Itoh M, Li XQ, Yano A, Xie Q, Takeuchi Y (1998) Patterns of efferent lymphatics of the mouse testis. J Androl 19:466-472
65. Itoh M, Terayama H, Naito M, Ogawa Y, Tainosho S (2005) Tissue microcircumstances for leukocytic infiltration into the testis and epididymis in mice. J Reprod Immunol 67:57-67
66. Jacobo P, Guazzone VA, Jarazo-Dietrich S, Theas MS, Lustig L (2009) Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis. J Reprod Immunol 81:44-54
67. Jean-Faucher C, Berger M, de Turckheim M, Veyssiere G, Jean C (1985) Testosterone and dihydrotestosterone levels in the epididymis, vas deferens and preputial gland of mice during sexual maturation. Int J Androl 8:44-57
68. Kern S, Robertson SA, Mau VJ, Maddocks S (1995) Cytokine secretion by macrophages in the rat testis. Biol Reprod 53:1407-1416
69. Kerr JB, Loveland KL, O'Bryan MK, de Kretser DM (2006) Cytology of the testis and intrinsic control mechanisms. In: Neill JD (ed) Knobil and Neill's physiology of reproduction. Elsevier, Amsterdam, pp 827-947
70. Kim TH, Hargreaves HK, Chan WC, Brynes RK, Alvarado C, Woodard J, Ragab AH (1986) Sequential testicular biopsies in childhood acute lymphocytic leukemia. Cancer 57:1038-1041
71. Kim Y, Turner D, Nelson J, Dobrinski I, McEntee M, Travis AJ (2008) Production of donorderived sperm after spermatogonial stem cell transplantation in the dog. Reproduction 136:823-831
72. Knee RA, Hickey DK, Beagley KW, Jones RC (2005) Transport of IgG across the blood-luminal barrier of the male reproductive tract of the rat and the effect of estradiol administration on reabsorption of fluid and IgG by the epididymal ducts. Biol Reprod 73:688-694
73. Kohno S, Munoz JA, Williams TM, Teuscher C, Bernard CC, Tung KS (1983) Immunopathology of murine experimental allergic orchitis. J Immunol 130:2675-2682
74. Koskimies AI, Kormano M, Lahti A (1971) A difference in the immunoglobulin content of seminiferous tubule fluid and rete testis fluid of the rat. J Reprod Fertil 27:463-465
75. Kriegel MA, Lohmann T, Gabler C, Blank N, Kalden JR, Lorenz HM (2004) Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med 199:1285-1291
76. Krieger JN (1984) Epididymitis, orchitis, and related conditions. Sex Transm Dis 11:173-181
77. Lee HM, Oh BC, Lim DP, Lee DS, Cho J, Lee G, Lee JR (2007) Role of complement regulatory proteins in the survival of murine allo-transplanted Sertoli cells. J Korean Med Sci 22:277-282
78. Lenzi A, Gandini L, Lombardo F, Rago R, Paoli D, Dondero F (1997) Antisperm antibody detection: 2. Clinical, biological, and statistical correlation between methods. Am J Reprod Immunol 38:224-230
79. Li H, Ren J, Dhabuwala CB, Shichi H (1997) Immunotolerance induced by intratesticular antigen priming: expression of TGF-b, Fas and Fas ligand. Ocul Immunol Inflamm 5:75-84
80. Li X, Strauss L, Kaatrasalo A, Mayerhofer A, Huhtaniemi I, Santti R, Mäkelä S, Poutanen M (2006) Transgenic mice expressing P450 aromatase as a model for male infertility associated with chronic inflammation in the testis. Endocrinology 147:1271-1277
81. Linnet L (1983) Clinical immunology of vasectomy and vasovasostomy. Urology 22:101-114
82. Lipscomb HL, Gardner PJ, Sharp JG (1979) The effect of neonatal thymectomy on the induction of autoimmune orchitis in rats. J Reprod Immunol 1:209-217
83. Maclaren N, Chen QY, Kukreja A, Marker J, Zhang CH, Sun ZS (2001) Autoimmune hypogonadism as part of an autoimmune polyglandular syndrome. J Soc Gynecol Investig 8:S52-54
84. Maddocks S, Setchell BP (1988) The rejection of thyroid allografts in the ovine testis. Immunol Cell Biol 66:1-8
85. Mahi-Brown CA, Tung KS (1989) Activation requirements of donor T cells and host T cell recruitment in adoptive transfer of murine experimental autoimmune orchitis (EAO). Cell Immunol 124:368-379
86. McClinton S, Eremin O, Miller ID (1990) Inflammatory infiltrate in prostatic hyperplasia- evidence of a host response to intraprostatic spermatozoa? Br J Urol 65:606-610
87. McLay RN, Banks WA, Kastin AJ (1997) Granulocyte macrophage-colony stimulating factor crosses the blood-testis barrier in mice. Biol Reprod 57:822-826
88. Meinhardt A, Bacher M, Metz C, Bucala R, Wreford N, Lan H, Atkins R, Hedger M (1998) Local regulation of macrophage subsets in the adult rat testis: examination of the roles of the seminiferous tubules, testosterone, and macrophage-migration inhibitory factor. Biol Reprod 59:371-378
89. Meng J, Holdcraft RW, Shima JE, Griswold MD, Braun RE (2005) Androgens regulate the permeability of the blood-testis barrier. Proc Natl Acad Sci USA 102:16696-16700
90. Meng J, Greenlee AR, Taub CJ, Braun RE (2011) Sertoli cell-specific deletion of the androgen receptor compromises testicular immune privilege in mice. Biol Reprod 85:254-260
91. Miller SC, Bowman BM, Rowland HG (1983) Structure, cytochemistry, endocytic activity, and immunoglobulin (Fc) receptors of rat testicular interstitial-tissue macrophages. Am J Anat 168:1-13
92. Mital P, Kaur G, Dufour J (2010) Immunoprotective Sertoli cells: Making allogeneic and xenogeneic transplantation feasible. Reproduction 139:495-504
93. Moller R (1980) Arrangement and fine structure of lymphatic vessels in the human spermatic cord. Andrologia 12:564-576
94. Mueller DL (2010) Mechanisms maintaining peripheral tolerance. Nat Immunol 11:21-27
95. Naito M, Itoh M (2008) Patterns of infiltration of lymphocytes into the testis under normal and pathological conditions in mice. Am J Reprod Immunol 59:55-61
96. Nasr IW, Wang Y, Gao G, Deng S, Diggs L, Rothstein DM, Tellides G, Lakkis FG, Dai Z (2005) Testicular immune privilege promotes transplantation tolerance by altering the balance between memory and regulatory T cells. J Immunol 174:6161-6168
97. Neaves WB, Billingham RE (1979) Transplantation of the testis. Transplantation 28:163-165
98. Nistal M, Paniagua R, Regadera J, Santamaria L, Amat P (1986) A quantitative morphological study of human Leydig cells from birth to adulthood. Cell Tissue Res 246:229-236
99. Nossal GJ (1994) Negative selection of lymphocytes. Cell 76:229-239
100. O'Bryan MK, Baker HW, Saunders JR, Kirszbaum L, Walker ID, Hudson P, Liu DY, Glew MD, d'Apice AJ, Murphy BF (1990) Human seminal clusterin (SP-40,40). Isolation and characterization. J Clin Invest 85:1477-1486
101. Okuma Y, Saito K, O'Connor AE, Phillips DJ, de Kretser DM, Hedger MP (2005) Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro. J Endocrinol 185:99-110
102. Osman DI, Plöen L (1978) The mammalian tubuli recti: ultrastructural study. Anat Rec 192:1-17
103. Pannek J, Haupt G (1997) Orchitis due to vasculitis in autoimmune diseases. Scand J Rheumatol 26:151-154
104. Paschke R, Bertelsbeck DS, Tsalimalma K, Nieschlag E (1994) Association of sperm antibodies with other autoantibodies in infertile men. Am J Reprod Immunol 32:88-94
105. Peirce EJ, Moore HD, Leigh CM, Breed WG (2003) Studies on sperm storage in the vas deferens of the spinifex hopping mouse (Notomys alexis). Reproduction 125:233-240
106. Pelletier RM (1986) Cyclic formation and decay of the blood-testis barrier in the mink (Mustela vison), a seasonal breeder. Am J Anat 175:91-117
107. Philip J, Selvan D, Desmond AD (2006) Mumps orchitis in the non-immune postpubertal male: a resurgent threat to male fertility? BJU Int 97:138-141
108. Plant TM, Wichel SF (2006) Puberty in nonhuman primates and humans. In: Neill JD (ed) Knobil and Neill's physiology of reproduction. Elsevier, Amsterdam, pp 2177-2230
109. Pöllänen P, Jahnukainen K, Punnonen J, Sainio-Pöllänen S (1992) Ontogeny of immunosuppressive activity, MHC antigens and leukocytes in the rat testis. J Reprod Immunol 21:257-274
110. Pöllänen P, Saari T, Yeung CH, Cooper TG (1995) Regulation of the transport of immunoglobulin G into the male rat reproductive tract. J Reprod Immunol 28:111-135
111. Raburn DJ, Coquelin A, Reinhart AJ, Hutson JC (1993) Regulation of the macrophage population in postnatal rat testis. J Reprod Immunol 24:139-151
112. Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kämpe O, Eskelin P, Pelto-Huikko M, Peltonen L (2002) Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet 11:397-409
113. Rettew JA, Huet-Hudson YM, Marriott I (2008) Testosterone reduces macrophage expression in the mouse of Toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod 78:432-437
114. Rival C, Lustig L, Iosub R, Guazzone VA, Schneider E, Meinhardt A, Fijak M (2006) Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis. Cell Tissue Res 324:311-318
115. Rival C, Guazzone VA, von Wulffen W, Hackstein H, Schneider E, Lustig L, Meinhardt A, Fijak M (2007) Expression of co-stimulatory molecules, chemokine receptors and proinflammatory cytokines in dendritic cells from normal and chronically inflamed rat testis. Mol Hum Reprod 13:853-861
116. Rivero VE, Motrich RD, Maccioni M, Riera CM (2007) Autoimmune etiology in chronic prostatitis syndrome: an advance in the understanding of this pathology. Crit Rev Immunol 27:33-46
117. Roper RJ, Doerge RW, Call SB, Tung KS, Hickey WF, Teuscher C (1998) Autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct lesions. Am J Pathol 152:1337-1345
118. Ryan AF, Grendell RL, Geraghty DE, Golos TG (2002) A soluble isoform of the rhesus monkey nonclassical MHC class I molecule Mamu-AG is expressed in the placenta and the testis. J Immunol 169:673-683
119. Salomon F, Saremaslani P, Jakob M, Hedinger CE (1982) Immune complex orchitis in infertile men. Immunoelectron microscopy of abnormal basement membrane structures. Lab Invest 47:555-567
120. Sanberg PR, Borlongan CV, Saporta S, Cameron DF (1996) Testis-derived Sertoli cells survive and provide localized immunoprotection for xenografts in rat brain. Nat Biotechnol 14:1692-1695
121. Sanberg PR, Saporta S, Borlongan CV, Othberg AI, Allen RC, Cameron DF (1997) The testisderived cultured Sertoli cell as a natural Fas-L secreting cell for immunosuppressive cellular therapy. Cell Transplant 6:191-193
122. Schuppe HC, Meinhardt A, Allam JP, Bergmann M, Weidner W, Haidl G (2008) Chronic orchitis:a neglected cause of male infertility? Andrologia 40:84-91
123. Selawry HP, Cameron DF (1993) Sertoli cell-enriched fractions in successful islet cell transplantation. Cell Transplant 2:123-129
124. Selawry HP, Whittington K (1984) Extended allograft survival of islets grafted into intraabdominally placed testis. Diabetes 33:405-406
125. Selawry HP, Whittington KB (1988) Prolonged intratesticular islet allograft survival is not dependent on local steroidogenesis. Horm Metab Res 20:562-565
126. Selawry HP, Kotb M, Herrod HG, Lu ZN (1991) Production of a factor, or factors, suppressing IL-2 production and T cell proliferation by Sertoli cell-enriched preparations. A potential role for islet transplantation in an immunologically privileged site. Transplantation 52:846-850
127. Setchell BP, Voglmayr JK, Waites GM (1969) A blood-testis barrier restricting passage from blood into rete testis fluid but not into lymph. J Physiol 200:73-85
128. Setchell BP, Uksila J, Maddocks S, Pöllänen P (1990) Testis physiology relevant to immunoregulation. J Reprod Immunol 18:19-32
129. Setchell BP, Granholm T, Ritzén EM (1995) Failure of thyroid allografts to function in the testes of cynomolgous monkeys. J Reprod Immunol 28:75-80
130. Sipione S, Simmen KC, Lord SJ, Motyka B, Ewen C, Shostak I, Rayat GR, Dufour JM, Korbutt GS, Rajotte RV, Bleackley RC (2006) Identification of a novel human granzyme B inhibitor secreted by cultured Sertoli cells. J Immunol 177:5051-5058
131. Skinner MK, Moses HL (1989) Transforming growth factor b gene expression and action in the seminiferous tubule: peritubular cell-Sertoli cell interactions. Mol Endocrinol 3:625-634
132. Slukvin II, Watkins DI, Golos TG (1999) Tissue distribution of the mRNA for a rhesus monkey major histocompatibility class Ib molecule, Mamu-AG. Tissue Antigens 53:282-291
133. Sonoda KH, Stein-Streilein J (2002) Ocular immune privilege and CD1d-reactive natural killer T cells. Cornea 21:S33-38
134. Sorrentino C, Silvestrini B, Braghiroli L, Chung SS, Giacomelli S, Leone MG, Xie Y, Sui Y, Mo M, Cheng CY (1998) Rat prostaglandin D2 synthetase: its tissue distribution, changes during maturation, and regulation in the testis and epididymis. Biol Reprod 59:843-853
135. Starace D, Galli R, Paone A, Cesaris PD, Filippini A, Ziparo E, Riccioli A (2008) Toll-like receptor 3 activation induces antiviral immune responses in mouse Sertoli cells. Biol Reprod 79:766-775
136. Statter MB, Foglia RP, Parks DE, Donahoe PK (1988) Fetal and postnatal testis shows immunoprivilege as donor tissue. J Urol 139:204-210
137. Suarez-Pinzon W, Korbutt GS, Power R, Hooton J, Rajotte RV, Rabinovitch A (2000) Testicular Sertoli cells protect islet b-cells from autoimmune destruction in NOD mice by a transforming growth factor-b1-dependent mechanism. Diabetes 49:1810-1818
138. Suzuki F, Nagano T (1986) Microvasculature of the human testis and excurrent duct system. Resin-casting and scanning electron-microscopic studies. Cell Tissue Res 243:79-89
139. Taguchi O, Nishizuka Y (1981) Experimental autoimmune orchitis after neonatal thymectomy in the mouse. Clin Exp Immunol 46:425-434
140. Tompkins AB, Hutchinson P, de Kretser DM, Hedger MP (1998) Characterization of lymphocytes in the adult rat testis by flow cytometry: effects of activin and transforming growth factor b on lymphocyte subsets in vitro. Biol Reprod 58:943-951
141. Tung K (1987) Immunologic basis of male infertility. Lab Invest 57:1-4
142. Tung KS, Alexander NJ (1980) Monocytic orchitis and aspermatogenesis in normal and vasectomized rhesus macaques (Macaca mulatta). Am J Pathol 101:17-30
143. Tung PS, Fritz IB (1984) Autoimmune orchitis can be induced by thymic lymphocytes autosensitized against syngeneic Sertoli cells in vitro. Biol Reprod 30:979-990
144. Tung KS, Unanue ER, Dixon FJ (1971) Pathogenesis of experimental allergic orchitis. II. The role of antibody. J Immunol 106:1463-1472
145. Tung KS, Smith S, Teuscher C, Cook C, Anderson RE (1987a) Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology. Am J Pathol 126:293-302
146. Tung KS, Yule TD, Mahi-Brown CA, Listrom MB (1987b) Distribution of histopathology and Ia positive cells in actively induced and passively transferred experimental autoimmune orchitis. J Immunol 138:752-759
147. Turner TT, Ewing LL, Jones CE, Howards SS, Zegeye B (1985) Androgens in various fluid compartments of the rat testis and epididymis after hypophysectomy and gonadotropin supplementation. J Androl 6:353-358
148. Veräjänkorva E, Setälä N, Teros T, Salmi AA, Pöllänen P (2002) Testicular-associated immune deviation: flushing of the testicular lymph sinusoids induces immunosuppression and inhibits formation of EAE in SJL mice. Scand J Immunol 55:478-483
149. Wang J, Wreford NG, Lan HY, Atkins R, Hedger MP (1994) Leukocyte populations of the adult rat testis following removal of the Leydig cells by treatment with ethane dimethane sulfonate and subcutaneous testosterone implants. Biol Reprod 51:551-561
150. Whitmore WF III, Gittes RF (1978) Intratesticular grafts: the testis as an exceptional immunologically privileged site. Trans Am Assoc Genitourin Surg 70:76-80
151. Whitmore WF III, Karsh L, Gittes RF (1985) The role of germinal epithelium and spermatogenesis in the privileged survival of intratesticular grafts. J Urol 134:782-786
152. Wichmann MW, Ayala A, Chaudry IH (1997) Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage. Am J Physiol 273:C1335-1340
153. Wilbanks GA, Mammolenti M, Streilein JW (1992) Studies on the induction of anterior chamberassociated immune deviation (ACAID). III. Induction of ACAID depends upon intraocular transforming growth factor-b. Eur J Immunol 22:165-173
154. Winnall WR, Ali U, O'Bryan MK, Hirst JJ, Whiley PA, Muir JA, Hedger MP (2007) Constitutive expression of prostaglandin-endoperoxide synthase 2 by somatic and spermatogenic cells is responsible for prostaglandin E2 production in the adult rat testis. Biol Reprod 76:759-768
155. Winnall WR, Muir JA, Hedger MP (2011) Rat resident testicular macrophages have an alternatively activated phenotype and constitutively produce interleukin-10 in vitro. J Leukoc Biol 90:133-143
156. Wyatt CR, Law L, Magnuson JA, Griswold MD, Magnuson NS (1988) Suppression of lymphocyte proliferation by proteins secreted by cultured Sertoli cells. J Reprod Immunol 14:27-40
157. Yule TD, Tung KS (1993) Experimental autoimmune orchitis induced by testis and sperm antigenspecific T cell clones: an important pathogenic cytokine is tumor necrosis factor. Endocrinology 133:1098-1107
158. Yule TD, Montoya GD, Russell LD, Williams TM, Tung KS (1988) Autoantigenic germ cells exist outside the blood testis barrier. J Immunol 141:1161-1167