Ocular immune privilege is circumvented by CD4+ T cells, leading to the rejection of intraocular tumors in an IFN-γ-dependent manner

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

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Although intraocular tumors reside in an immune-privileged site, they can circumvent immune privilege and undergo rejection, which typically follows one of two pathways. One pathway involves CD4+ T cells, delayed-type hypersensitivity (DTH), and the culmination in ischemic necrosis of the tumor and phthisis (atrophy) of the eye. The second pathway is DTH-independent and does not inflict collateral injury to ocular tissues, and the eye is preserved. In this study, we used a well-characterized tumor, Ad5E1, to analyze the role of IFN-γ in the nonphthisical form of intraocular tumor rejection. The results showed that IFN-γ induced tumor cell apoptosis, inhibited tumor cell proliferation, and promoted rejection by inhibiting angiogenesis. Microarray analysis revealed that IFN-γ induced up-regulation of five antiangiogenic genes and down-regulation of four proangiogenic genes in Ad5E1 tumor cells. Although IFN-γ knockout (KO) mice have progressively growing intraocular tumors, IFN-γ was not needed for the elimination of extraocular tumors, as all IFN-γ KO mice rejected s.c. tumor inocula. This represents a heretofore unrecognized role for IFN-γ in circumventing ocular immune privilege and eliminating intraocular tumors. The findings also reveal that some IFN-γ-independent tumor rejection processes are excluded from the eye and may represent a new facet of ocular immune privilege.

Original languageEnglish (US)
Pages (from-to)421-429
Number of pages9
JournalJournal of Leukocyte Biology
Volume81
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Angiogenesis
  • Anterior chamber

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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