TY - JOUR
T1 - CD8+ T cells circumvent immune privilege in the eye and mediate intraocular tumor rejection by a TNF-α-dependent mechanism
AU - Dace, Dru S.
AU - Chen, Peter W.
AU - Niederkorn, Jerry Y.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - Although intraocular tumors reside in an immune-privileged environment, T cells can circumvent immune privilege and mediate tumor rejection without inducing damage to normal ocular tissue. In this study, we used a well-characterized tumor, Ad5E1 (adenovirus type 5 early region 1), to analyze the role of CD8+ T cells in the pristine rejection of intraocular tumors. It has been previously documented that Ad5E1 tumor rejection can occur in the absence of CD8+ T cells. However, here we find that CD8 + T cells infiltrated intraocular Ad5E1 tumors in C57BL/6 mice. Surprisingly, CD8+ T cells from tumor-rejector mice could mediate intraocular tumor rejection following adoptive transfer to SCID mice. In determining the mechanisms behind CD8+ T cell-mediated tumor rejection, we discovered that antitumor CTL activity was neither observed nor necessary for rejection of the intraocular tumors. CD8+ T cells from rejector mice did not produce IFN-γ in response to Ad5E1 tumor Ags or use FasL to mediate intraocular tumor rejection. Also, CD8+ T cells did not use perforin or TRAIL, as CD8+ T cells from perforin knockout (KO) and TRAIL KO mice conferred protection to SCID recipient mice following adoptive transfer. We discovered that CD8+ T cells used TNF-α to mediate tumor rejection, because Ad5E1 tumor cells were highly sensitive to TNF-α-induced apoptosis and CD8+ T cells from TNF-α KO mice did not protect SCID mice from progressive Ad5E1 tumor growth. The results indicate that CD8+ T cells circumvent immune privilege and mediate intraocular tumor rejection by a TNF-α-dependent manner while leaving the eye intact and vision preserved.
AB - Although intraocular tumors reside in an immune-privileged environment, T cells can circumvent immune privilege and mediate tumor rejection without inducing damage to normal ocular tissue. In this study, we used a well-characterized tumor, Ad5E1 (adenovirus type 5 early region 1), to analyze the role of CD8+ T cells in the pristine rejection of intraocular tumors. It has been previously documented that Ad5E1 tumor rejection can occur in the absence of CD8+ T cells. However, here we find that CD8 + T cells infiltrated intraocular Ad5E1 tumors in C57BL/6 mice. Surprisingly, CD8+ T cells from tumor-rejector mice could mediate intraocular tumor rejection following adoptive transfer to SCID mice. In determining the mechanisms behind CD8+ T cell-mediated tumor rejection, we discovered that antitumor CTL activity was neither observed nor necessary for rejection of the intraocular tumors. CD8+ T cells from rejector mice did not produce IFN-γ in response to Ad5E1 tumor Ags or use FasL to mediate intraocular tumor rejection. Also, CD8+ T cells did not use perforin or TRAIL, as CD8+ T cells from perforin knockout (KO) and TRAIL KO mice conferred protection to SCID recipient mice following adoptive transfer. We discovered that CD8+ T cells used TNF-α to mediate tumor rejection, because Ad5E1 tumor cells were highly sensitive to TNF-α-induced apoptosis and CD8+ T cells from TNF-α KO mice did not protect SCID mice from progressive Ad5E1 tumor growth. The results indicate that CD8+ T cells circumvent immune privilege and mediate intraocular tumor rejection by a TNF-α-dependent manner while leaving the eye intact and vision preserved.
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U2 - 10.4049/jimmunol.178.10.6115
DO - 10.4049/jimmunol.178.10.6115
M3 - Article
C2 - 17475837
AN - SCOPUS:34248222156
SN - 0022-1767
VL - 178
SP - 6115
EP - 6122
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -