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Payal Khandelwal, Hyun Soo Lee, Simona L. Schlereth, Sharmila Masli, Daniel R. Saban; The Relevance Of Thrombospondin (TSP)-1 Expression By Antigen Presenting Cells In The Inhibition Of Experimental Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1126.
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TSP-1 is a matricellular protein with immunomodulatory properties. Our previous work showed that TSP-1 on antigen presenting cells (APC) inhibits the cells capacity to upregulate MHCII and B7, and thus suppresses T cell responses. We initiated work here to examine if APC derived TSP-1 can inhibit development of experimental allergic conjunctivitis (AC).
Ovalbumin (OVA)-primed T cells were magnetically sorted from mice 14d post immunization with 100ug OVA/ 300ng pertussis toxin/ 1mg aluminum hydroxide. Sorted T cells on Day 0 were adoptively transferred (10^6) into naïve wild-type (WT) vs. TSP-1 null mice, and subsequent challenges to these mice were administered by instillation of ovalbumin (OVA) loaded eye-drops (50ug/ul) once daily from Day 1 to 12. This system helps isolate the role of APC-T cell interactions involved in AC immunopathogenesis, since adoptively transferred T cells (without contributing B cells and IgE) largely depends on de novo re-simulation delivered by recipient APCs following topical challenge to induce AC. Post-challenge slit-lamp evaluation was performed daily to quantify severity of clinical signs. Two independent observers used a standardized grading system, which sums individual scores of 0 (normal) to 3+ (severe) for chemosis, redness, tearing and lid swelling. Naïve WT mice with adoptively transferred naïve T cells served as negative experimental control while naïve mice with no transferred T cells served as negative control.
No significant difference was detectable in the clinical scores of negative and experimental negative control mice (p>0.05) with a peak score of 5.5±0.2. In contrast, challenged WT mice transferred with OVA-primed T cells developed allergic symptoms with significantly increased clinical scores from day 7 and onward (p<0.05), with a peak score of 7.1±0.5. Interestingly, if the recipients of OVA-primed T cells were TSP-1 null, significant increases in clinical scores were detectable as early as day 4 and onward (p<0.05), and showed the highest peak score of 8.2±1.5
Early and more severe clinical response in TSP-1 null mice suggests that TSP-1 expression by APC in the conjunctiva plays a significant role in inhibiting the development of experimental AC.
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