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D.S. Dace, J.Y. Niederkorn; Non–Phthisical Rejection of Intraocular Tumors Does Not Require TRAIL–Mediated Apoptosis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1005.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine whether tumor necrosis factor–related apoptosis–inducing ligand (TRAIL) contributes to the rejection of the Ad5E1 murine tumor, a tumor normally rejected in C57BL/6 mice, but not in nude, CD4+ T cell depleted, or IFN–γ–/– mice. Methods: Intracameral injections of 3x105 Ad5E1 tumor cells were performed on C57BL/6 mice, B6 TRAIL–/– mice, B6 IFN–γ–/– mice, and B6 Beta–2 microglobulin knockout mice. Eyes were examined three times per week, and the tumor volume was recorded as the percentage of anterior chamber (AC) occupied with tumor. TRAIL knockout status was confirmed via PCR of tail snips. DTH assay was performed by the injection of mitomycin–C treated Ad5E1 cells into the ear pinnae of mice 37 days post–tumor injection. Antibody staining of Ad5E1 tumor cells was performed via FACS analysis. Results:C57BL/6 mice demonstrated similar kinetics of tumor rejection as previously seen. TRAIL–/– mice demonstrated accelerated rejection of the Ad5E1 tumor. Both IFN–γ–/– mice and Beta–2 microglobulin knockout mice failed to reject the tumor. DTH responses were absent in tumor rejecting C57BL/6 and TRAIL–/– mice, but present in non–rejecting IFN–γ–/– and Beta–2 microglobulin knockout mice. The Ad5E1 tumor cell stained positive for both MHC class I and class II, and interferon gamma treatment greatly enhanced expression of MHC class I. Conclusions: TRAIL is not responsible for the non–phthisical rejection of this tumor in C57BL/6 mice. However, the accelerated rejection of the tumor seen in TRAIL–/– mice suggests that TRAIL may play a role in maintaining immune privilege of the eye, specifically against T cells. The development of tumor specific DTH does not correlate with rejection of the tumor. Interferon gamma may play a role in the rejection of this tumor by not directly killing the tumor but indirectly through enhancing MHC class I expression and increasing their susceptibility to CD8+ T cell–mediated rejection. These results also demonstrate that CD8+ T cells and MHC class I may play a much larger role in the rejection of this tumor than previously considered.
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