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Simona L. Schlereth, Hyun Soo Lee, Daniel R. Saban; Relevance Of Low-dose Allergen Exposure In The Immunopathogenesis Of Experimental Allergic Conjunctivitis (AC). Invest. Ophthalmol. Vis. Sci. 2011;52(14):6420.
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Allergen exposure dose is an important factor that influences the initiation of allergic immunity. It is thought that low-dose, but not high-dose, allergen exposure is paramount to induce T helper 2 lymphocytes responsible for mediating allergy; however whether this is relevant in allergic conjunctivitis is incompletely understood.
To evaluate this in experimental AC, C57BL/6 mice were immunized with various doses and frequencies of ovalbumin allergen (OVA), suspended in a constant dose of aluminum hydroxide (alum; 1mg) plus pertussis toxin (Ptx; 300ng). Mice received this immunization with 100ug of OVA on day -14, and then boosted (or sham immunized with PBS) on day -7. In another experiment, mice were immunized once on day -14 with 10ug, 100ug, or 1000ug of OVA. All mice, including a naïve control, on day 0 were subjected to a topical challenge with OVA eye drops (50ug/ul), and these challenges were subsequently given once daily out to at least day 12. Development of AC was scored daily post-challenge via slit-lamp assessment of clinical signs (e.g., chemosis, redness, tearing, lid swelling). In addition, on day -1, serum was collected from mice for quantitation of OVA specific IgE levels.
Single immunization, rather than 2 immunizations, with 100ug of OVA led to stronger development of AC. This was indicated by higher IgE levels in once vs. twice immunized mice (10,000 vs. 8,000 pg/ml), and corroborated by considerable increases in clinical signs as well. Furthermore, comparisons of single immunization doses demonstrated that as low as a 10ug OVA immunization led to clinical scores equivalent to mice immunized with 100ug OVA (p>0.1). In contrast, mice immunized with 1000ug OVA had significantly lower clinical scores (p<0.05), which were, strikingly, similar in levels to naive mice that received topical OVA challenges (p>0.1).
These data suggest that low-dose, but not high-dose, exposure to allergen is critical in the development of experimental AC. These findings may be important in further understanding the immunopathogenesis of AC.
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