May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Tumor Infiltrating CD8+ T Cells Mediate Non-Phthisical Intraocular Tumor Rejection by a TNF- Dependent Mechanism
Author Affiliations & Notes
  • P. W. Chen
    Ophthalmology, Univ Texas Southwestern Medical Center, Dallas, Texas
  • D. S. Dace
    Ophthalmology, Washington University School of Medicine, St. Louis, Missouri
  • H. Alizadeh
    Ophthalmology, Univ Texas Southwestern Medical Center, Dallas, Texas
  • J. Y. Niederkorn
    Ophthalmology, Univ Texas Southwestern Medical Center, Dallas, Texas
  • Footnotes
    Commercial Relationships  P.W. Chen, None; D.S. Dace, None; H. Alizadeh, None; J.Y. Niederkorn, None.
  • Footnotes
    Support  NIH EY05631, EY016664 and an unrestricted grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2397. doi:https://doi.org/
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      P. W. Chen, D. S. Dace, H. Alizadeh, J. Y. Niederkorn; Tumor Infiltrating CD8+ T Cells Mediate Non-Phthisical Intraocular Tumor Rejection by a TNF- Dependent Mechanism. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2397. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : CD4+ T cells mediate a pristine, non-phthisical rejection of adenovirus type 5 early region 1-transformed embryonic tumors (Ad5E1) in an IFN-γ dependent antitumor response. Interestingly, CD8+ T cells also infiltrate intraocular Ad5E1 tumors. In this study, we analyzed CD8+ T cells in the Ad5E1 tumor model to determine their role in mediating non-phthisical intraocular tumor rejection.

Methods: : Mice were injected in the anterior chamber with the Ad5E1 tumor cells and tumor growth was recorded for 4 weeks. Pure CD8+ T cell populations were obtained by MACS magnetic bead separation followed by anti-CD4 antibody treatment and rabbit complement. Tumor infiltrating T cells were identified by FACS using T cell-specific antibodies. CTL activity was assessed using splenocytes co-cultured with Mitomycin C treated tumor cells in standard 4h 51Cr CTL assays. Ad5E1 MHC class I expression was analyzed by FACS analysis using MHC class I specific antibodies. Cytokine quantitation was assessed by ELISA. Apoptosis was evaluated using Annexin V staining.

Results: : Adoptive transfer of purified CD8+ T cells from B6 mice that previously rejected an intraocular tumor into SCID mice conferred protective immunity against an intraocular Ad5E1 tumor challenge. Interestingly, CD8+ mediated tumor cytotoxicity was not due to conventional CTL lysis even though Ad5E1 cells expressed MHC class I molecules. CD8+ T cells did not utilize perforin, IFN-γ, FasL, or TRAIL to mediate tumor rejection. Intraocular Ad5E1 tumors were rejected in TNF-α KO mice. However, SCID mice that received an adoptive transfer of purified CD8+ T cells from TNF-α KO rejector mice failed to reject intraocular Ad5E1 tumors.

Conclusions: : CD8+ T cells from B6 mice that reject intraocular Ad5E1 tumors have the capacity to elicit antitumor immunity. However, the CD8+ T cells do not eliminate tumor by conventional CTL mediated lysis, but employ a TNF-α mediated pathway to promote tumor rejection. Together, the data suggests that pristine, non-phthisical Ad5E1 tumor rejection involves a primary IFN-γ dependent CD4+ T cell pathway and a secondary TNF-α dependent CD8+ T cell pathway to mediate rejection of Ad5E1 ocular tumors without sustaining damage to the surrounding ocular tissues.

Keywords: immune tolerance/privilege • tumors 
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