Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1987 Sep;69(3):591–600.

EAU in the guinea pig: inhibition of cell-mediated immunity and Ia antigen expression by cyclosporin A.

J Liversidge 1, A W Thomson 1, H F Sewell 1, J V Forrester 1
PMCID: PMC1542386  PMID: 3478162

Abstract

Guinea pigs were immunized subcutaneously with highly purified bovine retinal S antigen (SAg) in complete Freund's adjuvant and treated from day 0 with cyclosporin A (CsA; 25 mg/kg by mouth) or drug vehicle. Skin tests carried out at 7 and 13 days showed maximal reactions to SAg at 24 h; at 13 days, however, strong, early, 'Arthus'-like responses to SAg were also recorded. CsA profoundly reduced DTH skin reactions to SAg and PPD, and prevented vitreal inflammation assessed at 17 days and retinal damage. Lymphocytes from the draining lymph nodes but not spleens of immunized guinea pigs showed a proliferative response to SAg which was suppressed by CsA administration. Responses to PHA, Con A or LPS were not so affected. Immunohistochemical staining (alkaline phosphatase-anti-alkaline phosphatase; APAAP) of the eye with newly available monoclonal antibodies to guinea pig T lymphocytes revealed a predominantly T cytotoxic/suppressor cell (Tc/s) infiltrate of the choroid and retina. CsA administration did not affect choroidal infiltration of Tc/s cells but markedly inhibited Ia antigen expression.

Full text

PDF
591

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoniou A. V., Parker D., Turk J. L., Tan B. T., Scheper R. J. Immunocytochemical identification and quantitation of mononuclear cells in the meninges during the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the guinea pig. Cell Immunol. 1986 Feb;97(2):386–396. doi: 10.1016/0008-8749(86)90408-9. [DOI] [PubMed] [Google Scholar]
  2. Borthwick G. M., Forrester J. V. Purification of retinal S-antigen by ion-exchange chromatography and chromatofocusing. Exp Eye Res. 1983 Dec;37(6):613–625. doi: 10.1016/0014-4835(83)90136-7. [DOI] [PubMed] [Google Scholar]
  3. Chan C. C., Detrick B., Nussenblatt R. B., Palestine A. G., Fujikawa L. S., Hooks J. J. HLA-DR antigens on retinal pigment epithelial cells from patients with uveitis. Arch Ophthalmol. 1986 May;104(5):725–729. doi: 10.1001/archopht.1986.01050170115034. [DOI] [PubMed] [Google Scholar]
  4. Chan C. C., Hooks J. J., Nussenblatt R. B., Detrick B. Expression of Ia antigen on retinal pigment epithelium in experimental autoimmune uveoretinitis. Curr Eye Res. 1986 Apr;5(4):325–330. doi: 10.3109/02713688609020059. [DOI] [PubMed] [Google Scholar]
  5. Faure J. P. Autoimmunity and the retina. Curr Top Eye Res. 1980;2:215–302. [PubMed] [Google Scholar]
  6. Forrester J. V., Borthwick G. M., McMenamin P. G. Ultrastructural pathology of S-antigen uveoretinitis. Invest Ophthalmol Vis Sci. 1985 Sep;26(9):1281–1292. [PubMed] [Google Scholar]
  7. Halloran P. F., Wadgymar A., Autenried P. Inhibition of MHC product induction may contribute to the immunosuppressive action of ciclosporin. Prog Allergy. 1986;38:258–268. [PubMed] [Google Scholar]
  8. Kupiec-Weglinski J. W., Filho M. A., Strom T. B., Tilney N. L. Sparing of suppressor cells: a critical action of cyclosporine. Transplantation. 1984 Aug;38(2):97–101. doi: 10.1097/00007890-198408000-00001. [DOI] [PubMed] [Google Scholar]
  9. Mochizuki M., Kuwabara T., McAllister C., Nussenblatt R. B., Gery I. Adoptive transfer of experimental autoimmune uveoretinitis in rats. Immunopathogenic mechanisms and histologic features. Invest Ophthalmol Vis Sci. 1985 Jan;26(1):1–9. [PubMed] [Google Scholar]
  10. Mochizuki M., Nussenblatt R. B., Kuwabara T., Gery I. Effects of cyclosporine and other immunosuppressive drugs on experimental autoimmune uveoretinitis in rats. Invest Ophthalmol Vis Sci. 1985 Feb;26(2):226–232. [PubMed] [Google Scholar]
  11. Nussenblatt R. B., Gunn H. C., Ryffel B., Borel J. F. Experimental autoimmunity. Prog Allergy. 1986;38:159–180. [PubMed] [Google Scholar]
  12. Nussenblatt R. B., Rodrigues M. M., Salinas-Carmona M. C., Gery I., Cevario S., Wacker W. Modulation of experimental autoimmune uveitis with cyclosporin A. Arch Ophthalmol. 1982 Jul;100(7):1146–1149. doi: 10.1001/archopht.1982.01030040124022. [DOI] [PubMed] [Google Scholar]
  13. Nussenblatt R. B., Salinas-Carmona M., Waksman B. H., Gery I. Cyclosporin A: alterations of the cellular immune response in S-antigen-induced experimental autoimmune uveitis. Int Arch Allergy Appl Immunol. 1983;70(4):289–294. doi: 10.1159/000233339. [DOI] [PubMed] [Google Scholar]
  14. Palestine A. G., Austin H. A., Nussenblatt R. B. Cyclosporine-induced nephrotoxicity in patients with autoimmune uveitis. Transplant Proc. 1985 Aug;17(4 Suppl 1):209–214. [PubMed] [Google Scholar]
  15. Rao N. A., Wacker W. B., Marak G. E., Jr Experimental allergic uveitis: clinicopathologic features associated with varying doses of S antigen. Arch Ophthalmol. 1979 Oct;97(10):1954–1958. doi: 10.1001/archopht.1979.01020020402028. [DOI] [PubMed] [Google Scholar]
  16. Rozenszajn L. A., Muellenberg-Coulombre C., Gery I., el-Saied M., Kuwabara T., Mochizuki M., Lando Z., Nussenblatt R. B. Induction of experimental autoimmune uveoretinitis by T-cell lines. Immunology. 1986 Apr;57(4):559–565. [PMC free article] [PubMed] [Google Scholar]
  17. Salinas-Carmona M. C., Nussenblatt R. B., Gery I. Experimental autoimmune uveitis in the athymic nude rat. Eur J Immunol. 1982 Jun;12(6):480–484. doi: 10.1002/eji.1830120606. [DOI] [PubMed] [Google Scholar]
  18. Sewell H. F., Thomson A. W., Walker F., King G., Abramovich D. R. Major histocompatibility complex class II antigen (HLA-DR, DQ and DP) expression in human fetal skin. Tissue Antigens. 1986 Jul;28(1):41–45. doi: 10.1111/j.1399-0039.1986.tb00458.x. [DOI] [PubMed] [Google Scholar]
  19. Striph G., Doft B., Rabin B., Johnson B. Retina S antigen-induced uveitis. The efficacy of cyclosporine and corticosteroids in treatment. Arch Ophthalmol. 1986 Jan;104(1):114–117. doi: 10.1001/archopht.1986.01050130128036. [DOI] [PubMed] [Google Scholar]
  20. Tan B. T., Ekelaar F., Luirink J., Rimmelzwaan G., De Jonge A. J., Scheper R. J. Production of monoclonal antibodies defining guinea pig T-cell surface markers and a strain 13 Ia-like antigen: the value of immunohistological screening. Hybridoma. 1985 Summer;4(2):115–124. doi: 10.1089/hyb.1985.4.115. [DOI] [PubMed] [Google Scholar]
  21. Thomson A. W., Moon D. K., Geczy C. L., Nelson D. S. Cyclosporin A inhibits lymphokine production but not the responses of macrophages to lymphokines. Immunology. 1983 Feb;48(2):291–299. [PMC free article] [PubMed] [Google Scholar]
  22. Thomson A. W., Moon D. K., Inoue Y., Geczy C. L., Nelson D. S. Modification of delayed-type hypersensitivity reactions to ovalbumin in cyclosporin A-treated guinea-pigs. Immunology. 1983 Feb;48(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  23. Webster L. M., Thomson A. W. Cyclosporin A prevents suppression of delayed-type hypersensitivity in mice immunized with high-dose sheep erythrocytes. Immunology. 1987 Mar;60(3):409–414. [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES