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D. R. Saban, S. Masli, S. K. Chauhan, R. Dana; Regulation of Corneal Antigen Presenting Cell Function by Thrombospondin-1. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1198.
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An inflammatory insult via thermal cautery was administered to corneas of wild-type (WT) or TSP-1 null C57BL/6 mice (n=12 corneas per group). After one week, corneas were collected and digested enzymatically for FACS analysis of APC maturation markers (MHCII and CD86). Additionally harvested corneal APC were co-cultured in triplicate wells with allogeneic (BALB/c) T cells to evaluate IFN-y secretion via ELISPOT assay. Lastly, normal WT or TSP-1 null allografts (and WT isografts) were orthotopically placed on BALB/c hosts and graft survival was measured for 8 weeks via slit-lamp biomicroscopy (n=14 mice per group). High-risk recipient graft beds were utilized in this experiment for their ability to stimulate significant maturation of donor cornea APC and direct allostimulation of host T cells.
The frequency of mature APC (CD45+ MHCII+ CD86hi) from cauterized WT corneas was 2.1%, while 9.4% were found in cauterized TSP-1 null corneas. Moreover, mean spot size of IFN-y+ T cells was 4-fold higher with APC harvested from cauterized TSP-1 null corneas (p=0.02). Lastly, the onset of rejection of TSP-1 null allografts was faster and markedly higher than WT ones in the high-risk setting (p=0.035).
TSP-1 therefore appears to play an important role in regulating corneal immunity, and our data suggest that this is accomplished by maintaining corneal APC phenotypically and functionally immature.
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