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The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (Ia)-positive cells in the rat iris and choroid

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Abstract

⊎ Background: The presence of Ia-positive cells (MHC class II equivalent) has been previously reported in the iris and choroid of various species. They have been reported to have both round and dendritic morphologies; the latter may represent classic dendritic cells, potent antigen-presenting cells (APCs). It is possible that the dendritic-like cells play a important role in (auto)immune processes of uveal and other ocular tissues. Using the flat or whole mount technique, the distribution of Ia-positive cells in the rat iris and choroid was investigated following penetrating Keratoplasty (PKP) and following treatment with cyclosporin A (CsA). ⊎ Methods: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to the following groups: (i) operated, untreated (n=24); (ii) operated, CsA-treated (10 mg/kg i.m.;n=22). Controls were groups (iii) normal LW rats (n=13); (iv) unopcrated, CsA-treated (16 days' treatment;n=8); (v) anterior perforation of the anterior chamber (n=3); (vi) eight corneal sutures only (n=4); (vii) syngeneic operated (LW to LW;n=4). Animals of groups (i) and (ii) were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group i, day 13; group ii, day 16). Both eyes were enucleated, immediately fixed, and iris-choroid flat mounts were examined for Ia-positive cells using APAAP immunohistochemistry. ⊎ Results: In the normal Lewis rat iris, scattered Ia-positive cells of both nondendritic and dendritic morphology were observed. CsA treatment in the unoperated rat did not result in a significant decrease in the percentage of dendritic cells in the iris or choroid. Anterior chamber perforation, the placement of sutures in the cornea and syngeneic PKP resulted in a moderate increase in iris Ia-positive cells. Allogeneic transplantation resulted in a large increase in both types of Ia-positive cells, particularly on day 13 with corneal rejection. In group ii, an initial decrease in Ia-positive cells until day 13 was observed; upon rejection (day 16), the histological picture was similar to that of untreated animals. Alterations in the operated choroid were also apparent following CsA treatment. ⊎ Conclusion: Corneal transplantation in the Lewis rat results in an increase in Ia-positive cells in the iris; CsA therapy can delay but not prevent this reaction. Changes in choroidal Ia-positive cells following PKP were not apparent, their numbers being affected only by CsA treatment following grafting.

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References

  1. Abi-Hanna D, Wakefield D, Watkins S (1988) HLA antigens in ocular tissues. I. In vivo expression in human eyes. Transplantation 45:610–613

    Google Scholar 

  2. Abi-Hanna D, McCluskey P, Wakefield D (1989) HLA antigens in the iris and aqueous humor gamma interferon levels in anterior uveitis. Invest Ophthalmol Vis Sci 30:990–994

    Google Scholar 

  3. Bakker M, Kijlstra A (1985) The expression of HLA-antigens in the human anterior uvea. Curr Eye Res 4:599–604

    Google Scholar 

  4. Barker CF, Billingham BE (1977) Immunologically privileged sites. Adv Immunol 25:1–54

    Google Scholar 

  5. Baudouin C, Fredj-Reygrobellet D, Gastaud P, Lapalus P (1988) HLA DR and DQ distribution in normal human ocular structures. Curr Eye Res 7:903–911

    Google Scholar 

  6. Baudouin C, Fredj-Reygrobellet D, Jambou D, Gastaud P, Lapalus P (1990) HLA DR and DQ expression on human retinal pigment epithelial cells in vitro. Graefe's Arch Clin Exp Ophthalmol 228:86–89

    Google Scholar 

  7. Beschorner WE, Arenas OÀ (1991) Loss of medullary dendritic cells in the thymus after cyclosporine and irradiation. Cell Immunol 132:505–514

    Google Scholar 

  8. Bishara SA, Bishara AH, Brautbar C (1988) Zonal variation of HLA expression on human corneal epithelium. Cornea 7:252–256

    Google Scholar 

  9. Braciale TJ, Morrison LA, Seetwon MT, Sambrook J, Geshing MJ, Braciale VL (1987) Antigen presentation pathways to class I and class II MHC-restricted T lymphocytes. Immunol Rev 98:95–114

    Google Scholar 

  10. Callanan DG, Luckenbach MW, Fischer BJ, Peeler IS, Niederkorn JY (1989) Histopathology of rejected orthotopic corneal grafts in the rat. Invest Ophthalmol Vis Sci 30:413–424

    Google Scholar 

  11. Catty L, Van den Oord J, Foets B, Missotten (1991) Morphologic and immunophenotypic heterogeneity of corneal dendritic cells. Graefe's Arch Clin Exp Ophthalmol 229:182–185

    Google Scholar 

  12. Chan CC, Detrick B, Nussenblatt RB, Palestine AG, Fujikawa LS, Hooks JJ (1986) HLA DR antigens on retinal pigment epithelial cells form patients with uveitis. Arch Ophthalmol 104:725–729

    Google Scholar 

  13. Chan CC, Hooks JJ, Nussenblatt RB, Detrick B (1986) Expression of Ia antigen on retinal pigment epithelium in experimental autoimmune uveoretinitis. Curr Eye Res 5:325–332

    Google Scholar 

  14. Chan CC, Nussenblatt RB, Ni M, Li S, Mao W (1988) Immunohistochemical markers in the normal human epibulbar conjunctiva from fetus to adult. Arch Ophthalmol 106:215–217

    Google Scholar 

  15. Cordell J, Falini B, Erber WN, Ghosh AK, Abulaziz Z, MacDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229

    Google Scholar 

  16. Coupland SE, Penfold PL, Billson FA (1993) HLA-DR expression in the human foetal and adult trabecular meshwork. Invest Ophthalmol Vis Sci 34 [Suppl]:1386

    Google Scholar 

  17. Coupland SE, Penfold PL, Billson FA, Hoffmann F (1994) Immunohistochemistry study of the glaucomatous and normal human trabecular meshwork. German J Ophthalmol 3:168–174

    Google Scholar 

  18. Coupland SE, Penfold PL, Billson FA, Hoffmann F (1994) Hydrolase participation in allograft rejection in rat penetrating keratoplasty. Graefe' s Arch Clin Exp Ophthalmol

  19. Coupland SE, Klebe S, Karow AC, Krause L, Bartlett RR, Hoffmann F (1994) Leflunomide following penetrating keratoplasty in the rat. Graefe' s Arch Clin Exp Ophthalmol

  20. Daar AS, Fuggle SV, Fabre JW, Ting A, Morris PJ (1984) The detailed description of HLA-A, B, C antigens in normal human organs. Transplantation 38:287–292

    Google Scholar 

  21. Daar AS, Fuggle SV, Fabre JW, Ting A, Morris PJ (1984) The detailed description of MHC Class II antigens in normal human organs. Transplantation 38:293–298

    Google Scholar 

  22. Detrick B, Rodrigues M, Chan CC, Tso MOM, Hooks JJ (1986) Expression of HLA DR antigen on retinal pigment epithelial cells in retinitis pigmentosa. Am J Ophthalmol 101:584–590

    Google Scholar 

  23. de Waal EJ, Rademakers LHPM, Schuurman HJ, van Loveren H (1993) Ultrastructure of interdigitating cells in the rat thymus during cyclosporin A treatment. In: Kamperdijk EWA, Nieuwenhuis P, Hoefsmit ECM (eds) Dendritic cells in fundamental and clinical immunology. Plenum Press, New York London, pp 153–157

    Google Scholar 

  24. Donnelly JJ, Li W, Rockey JH, Prendergast RA (1985) Induction of class II (Ia) alloantigen expression on corneal endothelium in vivo and in vitro. Invest Ophthalmol Vis Sci 26:575–580

    Google Scholar 

  25. Flügel C, Kinne RW, Streilein JW, Lütjen-Drecoll E (1992) Distinctive distribution of HLA class II and bone marrow derived cells in the anterior segment of human eyes. Curr Eye Res 11:1173–1183

    Google Scholar 

  26. Forrester JV, McMenamin PG, Holthouse I, Lumsden L, Liversidge J (1994) Localization and characterization of major histocompatibility complex class II-positive cells in the posterior segment of the eye implications for induction of autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 35:64–77

    Google Scholar 

  27. Fujikawa LS, Haugen JP (1990) Immunopathology of vitreous and retinochoroidal biopsy in posterior uveitis. Ophthalmology 97:1644–1653

    Google Scholar 

  28. Fujikawa LS, Colvin RB, Bhan AK, et al. (1982) Expression of HLA-A/B/C and -DR locus antigens on epithelial, stroma and endothelial cells of the human cornea. Cornea 1:213–222

    Google Scholar 

  29. Fujikawa LS, Chan C-C, McAllister C, Gery I, Hooks JJ, Detrick B, Nussenblatt RB (1987) Retinal vascular endothelium expresses fibronectin and class II histocompatibility complex antigens in experimental autoimmune uveitis. Cell Immunol 106:139–150

    Google Scholar 

  30. Geppert TD, Lipsky PE (1989) Antigen presentation by cells that are not of bone marrow origin. Reg Immunol 2:60–71

    Google Scholar 

  31. Gillette TE, Chandler JW, Greiner JV (1982) Langerhans cells of the ocular surface. Ophthalmology 89:700–711

    Google Scholar 

  32. Gorer PA (1987) The genetic and antigenic basis for tumor transplantation. J Pathol Bacteriol 44:691–697

    Google Scholar 

  33. Groenewegen G, Buurman WA, Jeunhomme GMAA, van der Linden GJ (1985) Effect of cyclosporin on MHC class II antigen expression on arterial and venous endothelium of mouse skin allografts. Transplantation 40:21–25

    Google Scholar 

  34. Halloran PE, Wadeymar A, Autenried P (1986) Inhibition of MHC product induction may contribute to the immunosuppressive action of ciclosporin. Prog Allergy 38:258

    Google Scholar 

  35. Hamel CP, Detrick B, Hooks JJ (1990) Evaluation of Ia expression in rat ocular tissues following inoculation with interferon-gamma. Exp Eye Res 50:173–182

    Google Scholar 

  36. Helbig H, Gurley RC, Reichl RJ, Mahdi R, Nussenblatt RB, Palestine AG (1990) Induction of MHC class II antigen in cultured bovine ciliary epithelial cells. Graefe's Arch Clin Exp Ophthalmol 228:556–561

    Google Scholar 

  37. Holland EJ, Chan CC, Wetzig RP, Palestine AG, Nussenblatt RB (1991) Clinical and immunohistologic studies of corneal rejection in the rat penetrating keratoplasty model. Cornea 10:374–380

    Google Scholar 

  38. Kaiser-Kupfer MI, Chan CC, Rodrigues M, Datiles MB, Gahl WA (1987) Nephropathic cystinosis: immunohistochemical and histopathological studies of cornea, conjunctiva and iris. Curr Eye Res 6:617–622

    Google Scholar 

  39. Kim MK, Chan C-C, Nussenblatt RB, Palestine AG (1987) Pharmacological effects on the expression of Class II histocompatibility antigen in experimental endotoxin-induced uveitis. Clin Immunol Immunopathol 45:70–77

    Google Scholar 

  40. Kim MK, Palestine AG, Nussenblatt RB, Chan C-C (1987) Expression of class II antigen in endotoxin induced uveitis. Curr Eye Res 5:869–876

    Google Scholar 

  41. Klareskog L, Forsum U, Tjernlund UM, Rask L, Peterson PA (1979) Expression of Ia-antigen-like molecules on cells of the corneal epithelium. Invest Ophthalmol Vis Sci 18:310–313

    Google Scholar 

  42. Knisely TL, Anderson TM, Sherwood ME, Flotte TJ, Albert DM, Granstein RD (1991) Morphologic and ultrastructural examination of I-A+ cells in the murine iris. Invest Ophthalmol Vis Sci 2423–2431

  43. Kusada M, Gaspari AA, Chan C-C, Gery I, Katz SI (1989) Expression of Ia antigen by ocular tissues of mice treated with interferon gamma. Invest Ophthalmol Vis Sci 30:764–768

    Google Scholar 

  44. Latina M, Flotte T, Crean E, Sherwood ME, Granstein RD (1988) Immunohistochemical staining of the human anterior segment — evidence that resident cells play a role in immunologic responses. Arch Ophthalmol 106:95–99

    Google Scholar 

  45. Liew SCK, Penfold P, Provis JM, Madigan MC, Billson FA (1994) Modulation of MHC class II expression in the absence of lymphocytic infiltrates in Alzheimer's retinae. J Neuropathol Exp Neurol 53:150–157

    Google Scholar 

  46. Liversidge J, Thomson AW, Sewell HF, Forrester JV (1987) EAU in the guinea pig: inhibition of cell-mediated immunity and Ia antigen expression by cyclosporin A. Clin Exp Immunol 69:591–600

    Google Scholar 

  47. Liversidge J, Sewell HF, Thomson AW, Forrester JV (1988) Lymphokine-induced MHC class II antigen expression on cultured retinal pigment epithelial cells and the influence of cyclosporin A. Immunology 63:313–317

    Google Scholar 

  48. Lynch MG, Peeler JS, Brown RH, Niederkorn JY (1987) Expression of HLA class I and II antigens on cells of the human trabecular meshwork. Ophthalmology 94:851–857

    Google Scholar 

  49. Mayer DJ, Daar AS, Casey TA, Fabre JW (1983) Localisation of HLA-A, B, C and HLA-DR antigens in the human cornea: practical significance for grafting and HLA typing. Transplant Proc 15:126–129

    Google Scholar 

  50. McMenamin PG, Holthouse I (1992) Immunohistochemical characterisation of dendritic cells and macrophages in the aqueous outflow pathways of the rat eye. Exp Eye Res 55:315–324

    Google Scholar 

  51. McMenamin PG, Holthouse I, Holt PG (1992) Class II histocompatibilty complex (Ia) antigen-bearing dendritic cells within the iris and ciliary body of the rat eye: distribution, phenotype and relation to retinal microglia. Immunology 77:385–393

    Google Scholar 

  52. Murray PI, Mooy CM, Visser-de Jong E, Baarsma GS, de Vries J, de Jong PTVM, Kiljistra A (1990) Immunohistochemical analysis of iris biopsy specimens from patients with Fuchs' heterochromic cyclitis. Am J Ophthalmol 109:394–399

    Google Scholar 

  53. Natali PG, Russo C, Ng AK, Nicotra MR, Appolonj C, Pellegrino MA, Ferrone S (1983) Ontogeny of human ia antigens. Cell Immunol 73:385–396

    Google Scholar 

  54. Ni M, Chan CC, Nussenblatt RB, Shaozhen L, Mao W (1988) Iris inflammatory cells, fibronectin, fibrinogen and immunoglobulin in various ocular diseases. Arch Ophthalmol 106:392–395

    Google Scholar 

  55. Pels E, van der Gaag R (1984) HLA-A, B, C and HLA-DR antigens and dendritic cells in fresh and organ culture preserved corneas. Cornea 3:231–239

    Google Scholar 

  56. Penfold PL, Provis JM, Liew SCK (1993) Human retinal microglia express phenotypic characteristics in common with dendritic antigen-presenting cells. J Neuroimmunol 45:183–192

    Google Scholar 

  57. Pepose JS, Gardner KM, Nestor MS, Foos RY, Pettit TH (1985) Detection of HLA class I and II antigens in rejected human corneal grafts. Ophthalmology 92:1480–1484

    Google Scholar 

  58. Porter RR (1985) The complement components coded in the major histocompatibility complex and their biological activities. Immunol Rev 87:7–17

    Google Scholar 

  59. Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Ann Rev Immunol 9:271–296

    Google Scholar 

  60. Streilein JW, Bradley D (1991) Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products. Invest Ophthalmol Vis Sci 32:2700–2710

    Google Scholar 

  61. Streilein JW, Toews GB, Bergstresser PR (1979) Corneal allografts fail to express ia antigens. Nature 282:326–327

    Google Scholar 

  62. Streilein, JW, Wilbanks GA, Cousins SW (1992) Immunoregulatory mechanisms of the eye. J Neuroimmunol 39:185–200

    Google Scholar 

  63. Treseler PA, Foulks GN, Sanfilippo F (1984) The expression of HLA antigens by cells in the human cornea. Am J Ophthalmol 98:763–772

    Google Scholar 

  64. Tripathi BJ, Tripathi RC, Wong P, Raja S (1990) Expression of HLA by the human trabecular meshwork and corneal endothelium. Exp Eye Res 51:269–276

    Google Scholar 

  65. Tuft SJ, Hawkins P, McKenzie JL, Hart DNJ (1984) The localisation of histocompatibility antigens in human cornea. Trans Ophthalmol Soc NZ 36:36–37

    Google Scholar 

  66. Unanue ER, Allen PM (1987) The basis for the immunoregulatory role of macrophages and other accessory cells. Science 236:551–557

    Google Scholar 

  67. Vantrappen L, Geboes K, Missotten L, Maudgal PC, Desmet V (1985) Lymphocytes and Langerhans cells in the normal human cornea. Invest Ophthalmol Vis Sci 26:220–225

    Google Scholar 

  68. Vicente A, Varas A, Alonso L, Gomez de Moral M, Zapata AG (1994) Ontogeny of rat thymic dendritic cells. Immunology 82:75–81

    Google Scholar 

  69. Wang H-M, Kaplan HJ, Chan WC, Johnson M (1987) The distribution and ontogeny of MHC antigens in murine ocular tissue. Invest Ophthalmol Vis Sci 28:1383–1389

    Google Scholar 

  70. Whitsett CF, Stulting RD (1984) The distribution of HLA antigens on human corneal tissue. Invest Ophthalmol Vis Sci 25:519–24

    Google Scholar 

  71. Williams KA, Coster DJ (1985) Penetrating corneal transplantation in the inbred rat: a new model. Invest Ophthalmol Vis Sci 26:23–30

    Google Scholar 

  72. Williams KA, Ash JK, Coster DJ (1985) Histocompatibility antigen and passenger cell content of the normal and diseased human cornea. Transplantation 393:265–269

    Google Scholar 

  73. Williams KA, Standfield SD, Wing SJ, Barras CW, Mills RA, Comacchio RM, Coster DJ (1992) Patterns of corneal graft rejection in the rabbit and reversal of rejection with monoclonal antibodies. Transplantation 54:38–43

    Google Scholar 

  74. Williamson IS, Streilein JW (1989) Induction of delayed hypersensitivity to alloantigens coinjected with Langerhans cells into the anterior chamber of the eye: abrogation of anterior chamber-associated immune deviation. Transplantation 47:519–524

    Google Scholar 

  75. Wong GHW, Clark-Lewis I, McKimm-Breskin JL, Harris AW, Schrader JW (1983) Interferon-γ induces enhanced expression of ia and H-2 antigens on B lymphoid, macrophage, and myeloid cell lines. J Immunol 131:788–793

    Google Scholar 

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  1. Augenabteilung, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, D-12200, Berlin, Germany

    Sarah E. Coupland, Lothar Krause & Friedrich Hoffmann

  2. Institut für Pathologie, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, D-12200, Berlin, Germany

    Sarah E. Coupland

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Coupland, S.E., Krause, L. & Hoffmann, F. The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (Ia)-positive cells in the rat iris and choroid. Graefe's Arch Clin Exp Ophthalmol 234, 116–124 (1996). https://doi.org/10.1007/BF00695251

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