The long-term objective of this study is to further define the regulatory processes governing ocular mucosal-associated immune responses and provide information applicable to the design of clinically relevant immunization protocols.
The specific aims -are: 1. to study the role of regulatory molecules in the induction of tear IgA antibody responses, 2. to delineate the mechanism(s) leading to IgA antibody expression in tears following ocular-topical (OT) application of soluble and particulate antigens and 3. to define the regulatory events influencing the appearance and retention of immunocompetent cells in mucosal-associated ocular compartments. All experiments will utilize the rat model, which has a well-characterized ocular mucosal-associated immune system. Cytokines with documented immunoglobulin enhancing activities will be tested for their capacity to stimulate IgA production in lacrimal gland tissue fragment cultures. Active cytokines will be tested for their regulatory influence on in vivo IgA antibody responses. The parameters influencing tear IgA antigen specific responses to anti-idiotypic reagents will be determined and the regulatory effect of anti-idiotypes on OT induced tear IgA responses assessed. Following OT administration .of soluble or particulate antigens, antigen dissemination and the appearance of antibody producing cells in lacrimal gland and conjunctiva will be studied. Marker coexpression in Thy-1 (OX7) bearing cell populations will be analyzed further using flow cytometry. Lacrimal gland lymphocyte subsets will be studied during both up and down- regulation. In situ labelling and adoptive transfer methods will be used to determine the origin of lymphoid subsets in both lacrimal and conjunctival tissues. The in vitro adherence of lymphocytes to lacrimal gland tissue will be further characterized, the phenotypes of adherent populations determined and the acinar cell culture system established. These studies will yield a more precise understanding of the nature of the lymphocyte-lacrimal gland interaction as well as establish its relationship to other adhesion systems. Overall, these investigations will provide a more complete understanding of the events involved in the regulation of ocular mucosal-associated antibody induction and yield new approaches to generate and control immune responses at the ocular surface.
| Ridley Lathers, D M; Gill, R F; Montgomery, P C (1998) Inductive pathways leading to rat tear IgA antibody responses. Invest Ophthalmol Vis Sci 39:1005-11 |
| Masinick, S A; Montgomery, C P; Montgomery, P C et al. (1997) Secretory IgA inhibits Pseudomonas aeruginosa binding to cornea and protects against keratitis. Invest Ophthalmol Vis Sci 38:910-8 |
| Carr, R M; Lolachi, C M; Albaran, R G et al. (1996) Nasal-associated lymphoid tissue is an inductive site for rat tear IgA antibody responses. Immunol Invest 25:387-96 |
