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CD8⁺ T Cells Circumvent Immune Privilege in the Eye and Mediate Intraocular Tumor Rejection by a TNF--Dependent Mechanism¹

Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390

Although intraocular tumors reside in an immune-privileged environment, T cells can circumvent immune privilege and mediate tumor rejection without inducing damage to normal ocular tissue. In this study, we used a well-characterized tumor, Ad5E1 (adenovirus type 5 early region 1), to analyze the role of CD8⁺ T cells in the pristine rejection of intraocular tumors. It has been previously documented that Ad5E1 tumor rejection can occur in the absence of CD8⁺ T cells. However, here we find that CD8⁺ T cells infiltrated intraocular Ad5E1 tumors in C57BL/6 mice. Surprisingly, CD8⁺ T cells from tumor-rejector mice could mediate intraocular tumor rejection following adoptive transfer to SCID mice. In determining the mechanisms behind CD8⁺ T cell-mediated tumor rejection, we discovered that antitumor CTL activity was neither observed nor necessary for rejection of the intraocular tumors. CD8⁺ T cells from rejector mice did not produce IFN- in response to Ad5E1 tumor Ags or use FasL to mediate intraocular tumor rejection. Also, CD8⁺ T cells did not use perforin or TRAIL, as CD8⁺ T cells from perforin knockout (KO) and TRAIL KO mice conferred protection to SCID recipient mice following adoptive transfer. We discovered that CD8⁺ T cells used TNF- to mediate tumor rejection, because Ad5E1 tumor cells were highly sensitive to TNF--induced apoptosis and CD8⁺ T cells from TNF- KO mice did not protect SCID mice from progressive Ad5E1 tumor growth. The results indicate that CD8⁺ T cells circumvent immune privilege and mediate intraocular tumor rejection by a TNF--dependent manner while leaving the eye intact and vision preserved.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work supported by National Institutes of Health Grants EY05631 and EY016664, and an unrestricted grant from Research to Prevent Blindness (New York, NY).

² Address correspondence and reprint requests to Dr. Jerry Y. Niederkorn, Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390. E-mail address: jerry.niederkorn{at}utsouthwestern.edu

³ Abbreviations used in this paper: AC, anterior chamber; Ad5E1, adenovirus type 5 early region 1; KO, knockout.