Rejection of intraocular tumors by CD4(+) T cells without induction of phthisis

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 -