Numerous clinical and experimental observations have suggested that the eye is an immunologically unique organ. We have endeavored to study the immunologic characteristics of the eye to better understand the immune pathogenesis of intraocular inflammatory disorders. In this regard we have studied the systemic immune response following the presentation of antigen via the anterior chamber (AC), a phenomenon termed anterior chamber-associated immune deviation (ACAID). The seminal observation in ACAID is that the systemic immune response is modulated by intraocular events following the entrance of antigen into the eye; e.g., as would occur in intraocular infectious diseases. Our recent studies have employed the hapten trinitrophenol (TNP) coupled to splenocytes or specific lymphocyte subsets to induce TNP-ACAID. The three features of ACAID which are central to the phenomenon are: systemic suppression of delayed-type hypersensitivity (DTH), enhanced antibody production, and normal T cell cytoxicity. We have demonstrated that suppression of DTH is: (1) mediated by a complex immunoregulatory network of T suppressor cells; (2) initiated by the elaboration of T suppressor inducer factor (TsIF) from the eye, which homes to the spleen; and (3) dependent upon the entrance of visible light into the eye. We propose to further our studies in this model system focusing on the suppression of DTH, the modulation of antibody production to TNP and the in vitro analysis of these events.
Our specific aims are: (1) the role of lymphokines/cytokines in the suppression of DTH in TNP-ACAID; (2) the in situ study of ocular immunoregulation of antibody production to TNP; (3) the in vitro study of ocular immunoregulation of antibody production to TNP.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY003723-09
Application #
3258140
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1981-05-01
Project End
1994-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Hooper, P; Bora, N S; Kaplan, H J et al. (1991) Inhibition of lymphocyte proliferation by resident ocular cells. Curr Eye Res 10:363-72
Ferguson, T A; Hayashi, J D; Kaplan, H J (1989) The immune response and the eye. III. Anterior chamber-associated immune deviation can be adoptively transferred by serum. J Immunol 143:821-6
Dutt, K; Waldrep, J C; Kaplan, H J et al. (1989) In vitro phenotypic and functional characterization of human pigment epithelial cell lines. Curr Eye Res 8:435-40
Kleiner, R C; Najarian, L V; Schatten, S et al. (1989) Vaso-occlusive retinopathy associated with antiphospholipid antibodies (lupus anticoagulant retinopathy). Ophthalmology 96:896-904
Wang, H M; Sheu, M M; Stulting, R D et al. (1989) Immunohistochemical evaluation of murine HSV-1 keratouveitis. Curr Eye Res 8:37-46
Wang, H M; Jeng, J E; Kaplan, H J (1989) Fc receptors in corneal epithelium. Curr Eye Res 8:123-30

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