CD8⁺ T cells circumvent immune privilege in the eye and mediate intraocular tumor rejection by a TNF-α-dependent mechanism

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-γ 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-α to mediate tumor rejection, because Ad5E1 tumor cells were highly sensitive to TNF-α-induced apoptosis and CD8⁺ T cells from TNF-α 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-α-dependent manner while leaving the eye intact and vision preserved.