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

Dru S. Dace, Peter W. Chen, Jerry Y. Niederkorn

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)6115-6122
Number of pages8
JournalJournal of Immunology
Volume178
Issue number10
StatePublished - May 15 2007

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T-Lymphocytes
Neoplasms
Adenoviridae
SCID Mice
Perforin
Adoptive Transfer
Knockout Mice
Rejection (Psychology)
Inbred C57BL Mouse
Apoptosis

ASJC Scopus subject areas

  • Immunology

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CD8+ T cells circumvent immune privilege in the eye and mediate intraocular tumor rejection by a TNF-α-dependent mechanism. / Dace, Dru S.; Chen, Peter W.; Niederkorn, Jerry Y.

In: Journal of Immunology, Vol. 178, No. 10, 15.05.2007, p. 6115-6122.

Research output: Contribution to journalArticle

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