Role of TRAIL and IFN-γ in CD4+ T cell-dependent tumor rejection in the anterior chamber of the eye

Shixuan Wang, Zita F H M Boonman, Hao Chuan Li, YuGuang He, Martine J. Jager, Rene E M Toes, Jerry Y. Niederkorn

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Although the anterior chamber of the eye expresses immune privilege, some ocular tumors succumb to immune rejection. Previous studies demonstrated that adenovirus-induced tumors, adenovirus type 5 early region 1 (Ad5E1), underwent immune rejection following transplantation into the anterior chamber of syngeneic mice. Intraocular tumor rejection required CD4+ T cells, but did not require the following: 1) CD8+ T cells, 2) B cells, 3) TNF, 4) perforin, 5) Fas ligand, or 6) NK cells. This study demonstrates that CD4+ T cell-dependent tumor rejection does not occur in IFN-γ-deficient mice. Ad5E1 tumor cells expressed DR5 receptor for TRAIL and were susceptible to TRAIL-induced apoptosis. Although IFN-γ did not directly induce apoptosis of the tumor cells, it rendered them 3-fold more susceptible to TRAIL-induced apoptosis. Both CD4+ T cells and corneal endothelial cells expressed TRAIL and induced apoptosis of Ad5E1 tumor cells. The results suggest that Ad5E1 tumor rejection occurs via TRAIL-induced apoptosis as follows: 1) tumor cells express TRAIL-R2 and are susceptible to TRAIL-induced apoptosis, 2) IFN-γ enhances TRAIL expression on CD4 + T cells and ocular cells, 3) IFN-γ enhances tumor cell susceptibility to TRAIL-induced apoptosis, 4) apoptotic tumor cells are found in the eyes of rejector mice, but not in the eyes of IFN-γ knockout mice that fail to reject intraocular tumors, 5) CD4+ T cells and corneal endothelial cells express TRAIL and induce apoptosis of tumor cells, and 6) apoptosis induced by either CD4+ T cells or corneal cells can be blocked with anti-TRAIL Ab.

Original languageEnglish (US)
Pages (from-to)2789-2796
Number of pages8
JournalJournal of Immunology
Issue number6
StatePublished - Sep 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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