The Journal of Immunology, Vol 151, Issue 10 5162-5171, Copyright © 1993 by American Association of Immunologists

ARTICLES

Evidence that peritoneal exudate cells cultured with eye-derived fluids are the proximate antigen-presenting cells in immune deviation of the ocular type

Y Hara, S Okamoto, B Rouse and JW Streilein
Department of Ophthalmology, Osaka University Medical School, Japan.

Immune privilege in the anterior chamber of the eye results in part from a selective deficit in delayed hypersensitivity that is elicited by antigenic materials placed in this unique tissue site. This distinctive systemic immune response to intraocular Ag (termed anterior chamber-associated immune deviation, ACAID) is fashioned by indigenous, intraocular bone marrow-derived cells that capture Ag within the anterior chamber and carry an Ag-specific ACAID-inducing signal via the blood directly to the spleen. An identical form of immune deviation can be evoked by the i.v. injection of peritoneal exudate cells (PEC) pulsed in vitro with soluble Ag in the presence of transforming growth factor-beta (TGF-beta). To determine whether eye-derived cells present Ag directly to responding splenic T cells or merely serve as vehicles to deliver Ag to the spleen, we have conducted MHC restriction experiments with PEC donors and recipients selected to differ at loci dictating MHC and/or minor histocompatibility Ag. When PEC were pulsed in vitro with soluble Ag (BSA) in the presence of culture fluid containing TGF-beta and injected into recipients with which they shared either class I or class II MHC molecules, BSA-specific ACAID was induced. By contrast, PEC pulsed with BSA and TGF-beta-containing culture fluid failed to induce ACAID when the cells were injected into recipients who were completely histoincompatible or were identical with the injected cells only at non-MHC loci. Using MHC class I-deficient transgenic mice, it was determined that intraocular injection of BSA failed to induce ACAID, and that class I-deficient PEC were incapable of inducing either BSA-specific ACAID or splenic regulatory T cells that suppress BSA-specific delayed hypersensitivity. We conclude that cells that carry an ACAID-inducing signal to the spleen are: 1) restricted in their ability to induce ACAID by MHC-encoded molecules, 2) these cells are the proximate APC ACAID, and 3) class I MHC molecules play a central role in presenting exogenous protein Ag to splenic T cells in ACAID.

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