TY - JOUR
T1 - Role of interferon-γ and cytotoxic T lymphocytes in intraocular tumor rejection
AU - Ligocki, Ann J.
AU - Brown, Joseph R.
AU - Niederkorn, Jerry Y.
N1 - Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2016/5
Y1 - 2016/5
N2 - 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.
AB - 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.
KW - CTL
KW - Eye
KW - IFN-γ
KW - Immune privilege
KW - Necrotic inflammation
UR - http://www.scopus.com/inward/record.url?scp=84964716245&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964716245&partnerID=8YFLogxK
U2 - 10.1189/jlb.3A0315-093RRR
DO - 10.1189/jlb.3A0315-093RRR
M3 - Article
C2 - 26578649
AN - SCOPUS:84964716245
SN - 0741-5400
VL - 99
SP - 735
EP - 747
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -