CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY Vol. 65,No. 3,December, pp. 294-299, 1992 Association between Mast Cells and the Development of Experimental Autoimmune Uveitis in Different Rat Strains QIANLI,YUJIROFUJINO,RACHEL R. CASPI,FATEMEHNAJAFIAN,ROBERT B. NUSSENBLA~, AND CHI-CHAOCHAN Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892 To study the role of anterior uveal mast cells in experi- mental autoimmune uveitis (EAU), the mast cells in the iris and ciliary body of Lewis rats, Brown Norway (BN) rats, and their Fl hybrids (LBNFl) were quantitated in normal rats and during the induction period of EAU. The mean baseline mast cell number was 68.9 f 10.8 per anterior uvea for Lewis rats, 0.3 + 0.2 for BN rats, and 4.6 + 0.6 for LBNFl rats. Detectable mast cells in the anterior uvea of S-Ag-immunized Lewis rats decreased to 60%of control at 6 days postimmunization, recovered to 80% at 10 days, and dropped again to 16%at 13 days, with disease onset around 14days. in Lewis rats that were adoptively transferred with a uveitogenic T-lymphocyte line, a profound drop in anterior uveal mast cell numbers occurred in the eyes with early signs of EAU, 3 days after the transfer. The decrease in detectable mast cells is consistent with mast cell degranu- lation. The data suggest that anterior mast cells participate in the immunopathogenesis of EAU and may influence the genetic susceptibility to EAU. D 1st~ Academic PM+, IM. INTRODUCTION Experimental autoimmune uveitis (EAU) is an or- gan-specific, T-cell-mediated autoimmune eye disease that has been used as an animal model for some forms of human uveitis (1). EAU can be induced by active immunization with retinal antigens, such as S-antigen (S-Ag) and th e interphotoreceptor retinoid-binding protein (IRBP), and can also be induced by adoptive transfer of retinal antigen-specific T lymphocytes, in- cluding long-term T-cell lines specific to uveitogenic peptide (l-3). The first histopathological findings of EAU in the rat are inflammatory cells in the anterior uvea and retinal vessels (4). Later the major part of the damage to the retina is caused by recruited leukocytes attracted to the eye through an amplification cascade initiated by the antigen-specific T cells. The mecha- nisms involved in this amplification have not been well defined, but are thought to induce cytokine-mediated as well as vascular effects. The relation between ocular tissue mast cells and EAU has been the subject of a number of studies in recent years (5-8). They have shown that there is a correlation between the number of choroidal mast cells and the susceptibility to EAU in different rat strains (5, 6), and that EAU can be delayed or suppressed by drugs that inhibit the release of mast cell mediators (7, 8). These findings suggest that local release of mast cell products is involved in the induction of EAU. Mast cell degranulation can be caused by receptor crosslinking via cytophilic antibodies and antigen, as well as by mediators released from activated T cells (9-12). Both mechanisms could be operative in EAU, since both cytophilic antibodies and autoimmune T lymphocytes are induced during the process of immu- nization cl,@. Mediators released from mast cells have been shown to directly increase vascular permeability (9). This effect could be particularly important in in- flammatory processes affecting closed organs such as the eye, where leukocytic infiltration must be preceded by a breakdown of the blood-organ barrier. In addition, mast cell mediators can induce expression of adhesion molecules on vascular endothelium and attract leuko- cytes to sites of inflammation (13-151, thus directly participating in the amplification cascade. We therefore decided to evaluate the number and the distribution of mast cells in the anterior uvea (the iris and ciliary body) of two inbred rat strains, EAU- susceptible Lewis rats and EAU-resistant BN rats, and their Fl hybrids. The present study examined the number of detectable mast cells in normal unmanipu- lated animals, and investigated the dynamic changes in mast cell numbers during the induction period of EAU. The results are consistent with the interpreta- tion that mast cells located in the anterior portion of the eye have a role in determining susceptibility to EAU and participate in the development of the disease. MATERIALSANDMETHODS Animals. A total of 184 female Lewis rats, BN rats, and their Fl hybrids (LBNFl) weighing 200 g (6-8 weeks of age) were obtained from Harlan Sprague- Dawley, Frederick, Maryland, and Charles River Ra- leigh, Raleigh, North Carolina. All animals were 294 0090-1229192 $4.00 C opyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.