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Philipp Steven, Sebastian Schwab, Daniel R Saban, Jerry Y Niederkorn, Uta Gehlsen; Role of Antigen-presenting Cells within Conjunctiva-associated Lymphoid Tissue in the Induction of Ocular Allergy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5576. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Organized conjunctiva-associated lymphoid tissue (CALT) is frequently present as lymphoid follicles in allergic eyes. However its potential role in the pathogenesis of ocular allergy has not been studied so far. This study was set up to investigate Antigen-presenting cells (APCs) within CALT in mouse models of ocular allergy to test the hypotheses that CALT demonstrates a disease-depending alteration and is involved in antigen-uptake and initiation of the local allergic immune response through APCs.
Two ocular allergy models (short-ragweed pollen and ovalbumin) were used. Number and size of CALT follicles were analyzed using immunohistochemistry of the nictitating membrane and compared with naïve animals. Antigen-uptake was investigated using topical fluorescent-labeled ovalbumin and E. coli. APCs within CALT were characterized by immunohistochemistry and flow cytometry. APCs within the nictitating membrane were depleted by subconjunctival injection of clodronate followed by sensitization, clinical allergy scoring and consecutive analysis of CALT. Finally B7.1 and B7.2 knockout mice were used and adoptive transfer experiments were performed to investigate the role of co-stimulatory molecules in ocular allergy.
Induction of ocular allergy leads to a significant increase in size and number of CALT. Whereas the number of T- and B-cells increased in the follicles, the number of macrophages and dendritic cells remained constant. Fluorescent-labeled ovalbumin and E. coli was taken up in CALT by CD11c+ and CD11b+ F4/80+ cells within 60 minutes. Depletion of APCs diminished CALT follicles and significantly reduces the clinical allergic score. B7.1/B7.2 knockout mice did not develop allergy, however allergy was restored by adoptive transfer of primed OVA-allergic CD4+ T-cells.
Conjunctiva-associated lymphoid tissue seems to play a central role in experimental ocular allergy demonstrated by its significant spatial expansion and take-up of soluble and particulate antigen through dendritic cells and macrophages. Furthermore, the presence of these cells is crucial for maintaining the spatial organization of CALT and also for a consecutive allergic response through co-stimulatory molecules B7.1/B7.2. These experiments form the basis for studies that focus on APCs within CALT as therapeutic targets for the prevention of ocular allergy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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