Role of interferon-γ and cytotoxic T lymphocytes in intraocular tumor rejection

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Abstract

The eye is normally an immunosuppressive environment. This condition is better known as immune privilege and protects the eye from immune-mediated inflammation of tissues that cannot regenerate. However, immune privilege creates a dilemma for the eye when intraocular neoplasms arise. In some cases, immune privilege is suspended, resulting in the immune rejection of intraocular tumors. This study employed a mouse model in which interferon-γ-dependent intraocular tumor rejection occurs. We tested the hypothesis that this rejection requires interferon-γ for the generation and functional capacity of cytotoxic T lymphocyte-mediated rejection of intraocular tumors. Tumors grew progressively in the eyes of interferon-γ knockout mice, even though the mice generated tumor-specific cytotoxic T lymphocyte responses in the periphery. However, interferon-γ knockout mice rejected tumors that were introduced into extraocular sites. Subcutaneous tumor immunization before intraocular challenge led to tumor rejection and preservation of the eye in wild-type mice. By contrast, tumors grew progressively in the eyes of interferon-γ knockout mice despite their ability to generate peripheral tumor-specific cytotoxic T lymphocytes as well as the capacity of CD8+ T cells to enter the eye as shown by the presence of CD8 and perforin message and CD3+CD8+ leukocytes within the tumor-bearing eye. We found that cytotoxic T lymphocytes generated in wild-type mice and adoptively transferred into interferon-γ knockout mice mediated the rejection of intraocular tumors in interferon-γ knockout hosts. The results indicate that interferon-γ is critical for the initial priming and differentiation of cytotoxic T lymphocytes residing in the periphery to produce the most effect antitumor functionwithin the eye.

Original languageEnglish (US)
Pages (from-to)735-747
Number of pages13
JournalJournal of Leukocyte Biology
Volume99
Issue number5
DOIs
Publication statusPublished - May 1 2016

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Keywords

  • CTL
  • Eye
  • IFN-γ
  • Immune privilege
  • Necrotic inflammation

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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