Reversal of CD8+ T cell ignorance and induction of anti-tumor immunity by peptide-pulsed APC.
In the present report, we have studied the potential of naive and activated effector CD8(+) T cells to function as anti-tumor T cells to a solid tumor using OVA-specific T cells from TCR-transgenic OT-I mice. Adoptive transfer of naive OT-I T cells into tumor-bearing syngeneic mice did not inhibit tumor cell growth. The adoptively transferred OT-I T cells did not proliferate in lymphoid tissue of tumor-bearing mice and were not anergized by the tumor. In contrast, adoptive transfer of preactivated OT-I CTL inhibited tumor growth in a dose-dependent manner, indicating that E.G7 was susceptible to immune effector cells. Importantly, naive OT-I T cells proliferated and elicited an anti-tumor response if they were adoptively transferred into normal or CD4-deficient mice that were then vaccinated with GM-CSF-induced bone marrow-derived OVA-pulsed APC. Collectively, these data indicate that even though naive tumor-specific T cells are present at a relatively high fraction they remain ignorant of the tumor and demonstrate that a CD8-mediated anti-tumor response can be induced by Ag-pulsed APC without CD4 T cell help.
Dalyot-Herman
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Department of Microbiology and Immunology and Department of Surgery, Division of Surgical Oncology, University of Miami School of Medicine, Miami, FL 33101, USA.
Bathe
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Malek
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D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004527:Egg Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D016219:Immunotherapy, Adoptive; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D013945:Thymoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin