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,
Departments of
*
Ophthalmology,
Immunohematology and Blood Transfusion, and
Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; and
Department of Immunology, Erasmus University Rotterdam and Academic Hospital Dijkzigt, Rotterdam, The Netherlands
Immune privilege of the eye protects against sight-threatening
inflammatory events, but can also permit outgrowth of otherwise
nonlethal immunogenic tumors. Nonetheless, ocular tumor growth can be
controlled by cellular immune responses. However, this will normally
result in phthisis of the eye, in case tumor rejection is mediated by a
delayed-type hypersensitivity response orchestrated by CD4+
T cells. We now show that intraocular tumors can be eradicated by
CD4+ Th cells without inducing collateral damage of
neighboring ocular tissue. Injection of tumor cells transformed by the
early region 1 of human adenovirus type 5 in the anterior chamber of
the eye leads to intraocular tumor formation. Tumor growth is transient
in immunocompetent mice, but lethal in immunodeficient nude mice,
indicating that T cell-dependent immunity is responsible for tumor
clearance. Tumor rejection has all the characteristics of a
CD8+ T cell-mediated immune response, as the tumor did not
express MHC class II and only tumor tissue was the subject of
destruction. However, analysis of the molecular and cellular mechanisms
involved in tumor clearance revealed that perforin, TNF-
, Fas
ligand, MHC class I, and CD8+ T cells did not play a
crucial role in tumor eradication. Instead, effective tumor rejection
was entirely dependent on CD4+ Th cells, as CD4-depleted as
well as MHC class II-deficient mice were unable to reject their
intraocular tumor. Taken together, these observations demonstrate that
CD4+ T cells are able to eradicate MHC class II-negative
tumors in an immune-privileged site without affecting surrounding
tissues or the induction of phthisis.
This article has been cited by other articles:
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  D. S. Dace, P. W. Chen, and J. Y. Niederkorn CD8+ T Cells Circumvent Immune Privilege in the Eye and Mediate Intraocular Tumor Rejection by a TNF-{alpha}-Dependent Mechanism J. Immunol., May 15, 2007; 178(10): 6115 - 6122. [Abstract] [Full Text] [PDF]
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 D. S. Dace, P. W. Chen, H. Alizadeh, and J. Y. Niederkorn Ocular immune privilege is circumvented by CD4+ T cells, leading to the rejection of intraocular tumors in an IFN-{gamma}-dependent manner J. Leukoc. Biol., February 1, 2007; 81(2): 421 - 429. [Abstract] [Full Text] [PDF]
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 Z. F. H. M. Boonman, L. R. H. M. Schurmans, N. van Rooijen, C. J. M. Melief, R. E. M. Toes, and M. J. Jager Macrophages are vital in spontaneous intraocular tumor eradication. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 2959 - 2965. [Abstract] [Full Text] [PDF]
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D. H. Schuurhuis, N. van Montfoort, A. Ioan-Facsinay, R. Jiawan, M. Camps, J. Nouta, C. J. M. Melief, J. S. Verbeek, and F. Ossendorp Immune complex-loaded dendritic cells are superior to soluble immune complexes as antitumor vaccine. J. Immunol., April 15, 2006; 176(8): 4573 - 4580. [Abstract] [Full Text] [PDF]
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 K. Hallermalm, A. De Geer, R. Kiessling, V. Levitsky, and J. Levitskaya Autocrine Secretion of Fas Ligand Shields Tumor Cells from Fas-Mediated Killing by Cytotoxic Lymphocytes Cancer Res., September 15, 2004; 64(18): 6775 - 6782. [Abstract] [Full Text] [PDF]
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S. Wang, Z. F. H. M. Boonman, H.-C. Li, Y. He, M. J. Jager, R. E. M. Toes, and J. Y. Niederkorn Role of TRAIL and IFN-{gamma} in CD4+ T Cell-Dependent Tumor Rejection in the Anterior Chamber of the Eye J. Immunol., September 15, 2003; 171(6): 2789 - 2796. [Abstract] [Full Text] [PDF]
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