Rejection of intraocular tumors by CD4(+) T cells without induction of phthisis
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Rejection of intraocular tumors by CD4(+) T cells without induction of phthisis. / Schurmans, L R; Diehl, L; den Boer, A T; Sutmuller, R P; Boonman, Z F; Medema, J P; van der Voort, E I; Laman, J; Melief, C J; Jager, M J; Toes, R E.
in: J IMMUNOL, Jahrgang 167, Nr. 10, 15.11.2001, S. 5832-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Rejection of intraocular tumors by CD4(+) T cells without induction of phthisis
AU - Schurmans, L R
AU - Diehl, L
AU - den Boer, A T
AU - Sutmuller, R P
AU - Boonman, Z F
AU - Medema, J P
AU - van der Voort, E I
AU - Laman, J
AU - Melief, C J
AU - Jager, M J
AU - Toes, R E
PY - 2001/11/15
Y1 - 2001/11/15
N2 - 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-alpha, 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.
AB - 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-alpha, 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.
KW - Adenovirus E1 Proteins
KW - Animals
KW - Anterior Chamber
KW - CD4-Positive T-Lymphocytes
KW - CD8-Positive T-Lymphocytes
KW - Cell Line, Transformed
KW - Eye Diseases
KW - Eye Neoplasms
KW - Fas Ligand Protein
KW - Inflammation
KW - Lymphocyte Depletion
KW - Male
KW - Membrane Glycoproteins
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Perforin
KW - Pore Forming Cytotoxic Proteins
KW - Tumor Necrosis Factor-alpha
M3 - SCORING: Journal article
C2 - 11698457
VL - 167
SP - 5832
EP - 5837
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 10
ER -