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Related Experiment Videos

Imposing deviant immunity on the presensitized state

M M Kosiewicz1, S Okamoto, S Miki

  • 1Department of Microbiology and Immunology, University of Miami School of Medicine, Fl.

Journal of Immunology (Baltimore, Md. : 1950)
|October 1, 1994
PubMed
Summary

Introducing antigen into the eye selectively suppresses delayed hypersensitivity (DH) in previously sensitized mice. This immune tolerance is mediated by regulatory CD8+ T cells, highlighting unique ocular immune strategies.

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Area of Science:

  • Immunology
  • Ocular Immunology
  • Immune Regulation

Background:

  • Delayed hypersensitivity (DH) is crucial for pathogen defense but can cause tissue damage, especially in the eye, potentially leading to blindness.
  • Intraocular antigen injection in naive mice induces a unique systemic immune response with suppressed DH, mediated by regulatory CD8+ T cells.

Purpose of the Study:

  • To investigate if antigen injection into the anterior chamber of the eye also suppresses DH in specifically sensitized mice.
  • To understand the mechanisms underlying ocular immune privilege and its potential for inducing tolerance in pre-immunized individuals.

Main Methods:

  • Mice were specifically sensitized to antigens (heterologous proteins, retinal autoantigens, minor histocompatibility antigens).
  • Antigens were injected into the anterior chamber of the eyes of sensitized mice.

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  • Suppression of DH was assessed.
  • Regulatory mechanisms involving CD8+ T cells and TGF-beta were investigated.
  • Attempts to induce tolerance via intravenous antigen injection or skin painting were performed.

    • Main Results:

    • Antigen injection into the anterior chamber significantly blunted or eliminated DH in previously sensitized mice.
    • Ag-specific CD8+ T cells were identified as the mediators of this suppression.
    • Intravenous injection of antigen-pulsed peritoneal exudate cells with TGF-beta could impose failed DH.
    • Tolerance could not be achieved in presensitized mice through systemic routes like intravenous antigen or skin painting.

    Conclusions:

    • The eye employs potent immune regulatory mechanisms to protect against inflammation, even in the context of pre-existing immunity.
    • Intraocular antigen administration can successfully induce DH suppression and tolerance in sensitized individuals.
    • These findings suggest unique ocular immune strategies for managing inflammation and establishing tolerance.