Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Immunological non-responsiveness and acquisition of tolerance in relation to immune privilege in the eye

Abstract

Immune privilege is a dynamic, physiological process that enables the eye to accept foreign tissue grafts in an unprecedented fashion. Privilege is actively acquired and maintained by immune regulatory forces that represent an important form of antigen-specific immunological tolerance. Privilege in the eye results from eye-dependent modifications in the induction (afferent limb) and expression (efferent limb) of immunity to intraocular antigens. The eye-dependent features that are important in privilege include integrity of the blood-ocular barrier, the virtual absence of lymphatics, an afferent drainage pathway that is almost exclusively via the blood vasculature, and an immunosuppressive intraocular microenvironment. This microenvironment is comprised of a variety of cytokines and neuropeptides that (1) impair antigen-driven activation of primed and alloreactive T cells, (2) suppress effector functions of activated macrophages, and (3) modify the antigen processing and presenting properties of indigenous, bone-marrow-derived professional antigen presenting cells. Eye-derived antigenic signals, which escape when local antigen presenting cells migrate via the blood to the spleen, selectively activate regulatory T cells that impair the development of antigen-specific delayed hypersensitivity and complement fixing antibodies, a phenomenon termed anterior chamber associated immune deviation (ACAID). ACAID has been implicated in the extraordinary success of orthotopic corneal allografts, as well as the prolonged intraocular survival enjoyed by transplants of retinal tissues. The active features of immune privilege can be exploited to secure successful corneal and retinal transplantation.

References

  1. Medawar P . Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol 1948;29:58–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Niederkorn JY . Immune privilege and immune regulation in the eye. Adv Immunol 1990;48:191–226.

    CAS  Article  Google Scholar 

  3. Streilein JW . Immune regulation and the eye: a dangerous compromise. FASEB J 1987;1:199–208.

    CAS  Article  Google Scholar 

  4. Cousins S, Trattler W, Streilein JW . Immune privilege and suppression of immunogenic inflammation in the anterior chamber of the eye. Curr Eye Res 1991;10:287–97.

    CAS  Article  Google Scholar 

  5. Sonoda Y, Streilein JW . Impaired cell mediated immunity in mice bearing healthy orthotopic corneal allografts. J Immunol 1993;150:1727–34.

    CAS  PubMed  Google Scholar 

  6. Jiang LQ, Streilein JW . Immunologic privilege evoked by histocompatible intracameral retinal transplants. Regional Immunol 1991;3:121–30.

    CAS  Google Scholar 

  7. Niederkorn J, Streilein JW, Shadduck JA . Deviant immune responses to allogeneic tumours injected intracamerally and subcutaneously in mice. Invest Ophthalmol Vis Sci 1980;20:355–63.

    Google Scholar 

  8. McLeish W, Rubsamen P, Atherton SS, Streilein JW . Immunobiology of Langerhans cells on the ocular surface. II. Role of central corneal Langerhans cells in stromal keratitis following experimental HSV-1 infection in mice. Regional Immunol 1989;2:236–43.

    CAS  Google Scholar 

  9. Streilein JW, Atherton S, Vann VA . Critical role for ACAID in the distinctive pattern of retinitis that follows anterior chamber inoculation of HSV-1. Curr Eye Res 1987;6:127–32.

    CAS  Article  Google Scholar 

  10. Hara Y, Caspi RR, Wiggert B, Chan C-C, Wilbanks GA, Streilein JW . Suppression of experimental autoimmune uveitis in mice by induction of Anterior Chamber Associated Immune Deviation with inter-photoreceptor retinoid binding protein. J Immunol 1992;148:1685–92.

    CAS  PubMed  Google Scholar 

  11. Williamson JSP, Bradley D, Streilein JW . Immunoregulatory properties of bone marrow derived cells in the iris and ciliary body. Immunology 1989;67:96–102.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. McMenamin PG, Hothouse I, Hot PG . Class II major histocompatibility complex (Ia) antigen-bearing dendritic cells within the iris and ciliary body of the rat eye: distribution, phenotype and relation to retinal microglia. Immunology 1992;77:385–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Wilbanks GA, Mammolenti MM, Streilein JW . Studies on the induction of Anterior Chamber Associated Immune Deviation (ACAID). II. Eye-derived cells participate in generating blood borne signals that induce ACAID. J Immunol 1991;146:3018–24.

    CAS  PubMed  Google Scholar 

  14. Streilein JW, Wilbanks GA, Cousins SW . Immunoregulatory mechanisms of the eye. J Neuroimmunol 1002;39:185–200.

    Article  Google Scholar 

  15. Knisely TL, Hosoi J, Nazareno R, Granstein R . Aqueous humour contains biologically significant concentrations of glucocorticoids but little or no cortisol binding globulin: relevance to immune privilege in the anterior chamber of the eye. Invest Ophthalmol Vis Sci 1994;35:3711–23.

    CAS  PubMed  Google Scholar 

  16. Kaplan HJ, Streilein JW . Immune response to immunisation via the anterior chamber of the eye. I. F1 lymphocyte induced-immune deviation. J Immunol 1977;118:809–14.

    CAS  PubMed  Google Scholar 

  17. Bando Y, Ksander BR, Streilein JW . Incomplete activation of lymphokine-producing T cells by alloantigenic intraocular tumours in ACAID. Immunology 1992;78:266–72.

    Google Scholar 

  18. Kosiewicz MM, Okamoto S, Miki S, Ksander BR, Shimizu T, Streilein JW . Imposing deviant immunity on the presensitised state. J Immunol 1994;153:2962–73.

    CAS  PubMed  Google Scholar 

  19. Jiang LQ, Jorquera M, Streilein JW . Subretinal space vitreous cavity as immunologically privileged sites for retinal allografts. Invest Ophthalmol Vis Sci 1993;34: 3347–54.

    CAS  PubMed  Google Scholar 

  20. Eichorn M, Horneber M, Streilein JW, Lutjen-Drecoll E . Anterior chamber associated immune deviation elicited via primate eyes. Invest Ophthalmol Vis Sci 1993;34:2926–30.

    Google Scholar 

  21. Wilbanks GA, Streilein JW . Studies on the induction of Anterior Chamber Associated Immune Deviation (ACAID). I. Evidence that an antigen-specific, ACAID-inducing, cell-associated signal exists in the peripheral blood. J Immunol 1991;146:2610–7.

    CAS  PubMed  Google Scholar 

  22. Wilbanks GA, Mammolenti MM, Streilein JW . Studies on the induction of Anterior Chamber-Associated Immune Deviation (ACAID). III. Induction of ACAID depends upon intraocular transforming growth factor-β. Eur J Immunol 1992;22:165–73.

    CAS  Article  Google Scholar 

  23. Wilbanks G, Streilein JW . Macrophages capable of inducing anterior chamber associated immune deviation demonstrate spleen-seeking migratory properties. Regional Immunol 1992;4:130–7.

    CAS  Google Scholar 

  24. Hara Y, Caspi RR, Wiggert B, Dorf M, Streilein JW . Analysis of an in vitro-generated signal that induces systemic immune deviation similar to that elicited by antigen injected into the anterior chamber of the eye. J Immunol 1992;149:1531–8.

    CAS  PubMed  Google Scholar 

  25. Hara Y, Okamoto S, Rouse B, Streilein JW . Evidence that pertioneal exudate cells cultured with eye-derived fluids are the proximate antigen presenting cells in immune deviation of the ocular type. J Immunol 1993;151:5162–71.

    CAS  PubMed  Google Scholar 

  26. Okamoto S, Hara Y, Streilein JW . Induction of anterior chamber associated immune deviation (ACAID) with lymphoreticular allogeneic cells. Transplantation 1995;59:377–81.

    CAS  PubMed  Google Scholar 

  27. Niederkorn JY, Streilein JW . Immunogenetic basis for immunologie privilege in the anterior chamber of the eye. Immunogenetics 1981;13:227–36.

    CAS  Article  Google Scholar 

  28. Jiang LQ, Jorquera M, Streilein JW . Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts. Exp Eye Res 1994;58:719–28.

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Streilein, J. Immunological non-responsiveness and acquisition of tolerance in relation to immune privilege in the eye. Eye 9, 236–240 (1995). https://doi.org/10.1038/eye.1995.46

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/eye.1995.46

Keywords

  • Anterior chamber associated immune deviation
  • Delayed hypersensitivity
  • Immune privilege
  • Immunosuppressive microenvironment

Further reading

Search

Quick links