The mechanisms involved in the immunopathology of recurrent uveitis are not yet clearly understood. Our hypothesis is that a small number of resident immunocompetent cells is responsible for amplification of the chronic ocular inflammatory response which is mainly composed of non-antigen-specific inflammatory cells. In the proposed investigations we will be concerned with two aspects which underlie this hypothesis: 1) the role of immunologically committed memory cells; and 2) the effects of membrane antigens, lymphokines, and cytokines in amplification of the inflammatory response. In the rabbit model system, we have recently published data confirming the presence of Macrophage Ia Recruiting Factor (MIRF) in the aqueous from uveitic eyes. The experiments proposed herein will investigate the intraocular production of a variety of lymphokines including IL-1, IL-2, and interferon in both primary and recurrent uveitis. In other experiments we will passively immunize the eye using syngeneic donor immune lymphocytes or lymphoid tissue. Under those circumstances, intravenous challenge with specific antigen in these otherwise naive recipients should result in uveitis. The time sequence for these experiments will allow us to mimic the striking immunologic memory associated with human recurrent ocular inflammatory disease. We also intend to block both the induction and recall phase of antigen-induced uveitis. First, we will attempt to inhibit the ability of the sensitized lymphocyte to produce lymphokine mediators, using the local infusion of pharmacological agents including theophylline to effectively block the amplifying effects emanating from these cells. In the second phase of these experiments on inhibition of uveitis, we hope to demonstrate that lipocortin, a phospholipase inhibitory protein, will have a marked anti-inflammatory effect. We postulate that lipocortin will locally inhibit the release of free arachadonic acid from phospholipids through the action of phospholipases and thus prevent prostaglandin synthesis.
| Kerlin, R L; Cebra, J J; Weinstein, P D et al. (1994) Sea star factor blocks development of T-dependent antibody secreting clones by preventing lymphokine secretion. Cell Immunol 156:62-76 |
| Jabs, D A; Burek, C L; Hu, Q et al. (1992) Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice. Cell Immunol 141:496-507 |
| Jabs, D A; Prendergast, R A (1991) Autoimmune ocular disease in MRL/Mp-lpr/lpr mice is suppressed by anti-CD4 antibody. Invest Ophthalmol Vis Sci 32:2718-22 |
| Jabs, D A; Enger, C; Prendergast, R A (1991) Murine models of Sjogren's syndrome. Evolution of the lacrimal gland inflammatory lesions. Invest Ophthalmol Vis Sci 32:371-80 |
| Jabs, D A; Prendergast, R A (1991) Ocular inflammation in MRL/Mp-lpr/lpr mice. Invest Ophthalmol Vis Sci 32:1944-7 |
| Cohan, V L; Scott, A L; Dinarello, C A et al. (1991) Interleukin-1 is a mucus secretagogue. Cell Immunol 136:425-34 |
| Taylor, H R; Whittum-Hudson, J; Schachter, J et al. (1988) Oral immunization with chlamydial major outer membrane protein (MOMP). Invest Ophthalmol Vis Sci 29:1847-53 |
| Liu, S H; Sakai, F; Prendergast, R A et al. (1987) Experimental autoimmune dacryoadenitis. II. Harderian gland disease in the rat. Invest Ophthalmol Vis Sci 28:276-80 |
| Young, E; Schachter, J; Prendergast, R A et al. (1987) The effect of cyclosporine in chlamydial eye infection. Curr Eye Res 6:683-9 |
| Whittum-Hudson, J A; Prendergast, R A; Taylor, H R (1987) Conjunctival immune responses to Chlamydia trachomatis: effects of oral preimmunization on conjunctival lymphocyte subsets. Adv Exp Med Biol 216B:1839-46 |
Showing the most recent 10 out of 19 publications
