Th2-type CD4+ cells neither enhance nor suppress antitumor CTL activity in a mouse tumor model.
Many cervical cancers express the E7 protein of human papillomavirus 16 as a tumor-specific Ag (TSA). To establish the role of E7-specific T cell help in CD8+ CTL-mediated tumor regression, C57BL/6J mice were immunized with E7 protein or with a peptide (GF001) comprising a minimal CTL epitope of E7, together with different adjuvants. Immunized mice were challenged with an E7-expressing tumor cell line, EL4.E7. Growth of EL4.E7 was reduced following immunization with E7 and Quil-A (an adjuvant that induced a Th1-type response to E7) or with GF001 and Quil-A. Depletion of CD8+ cells, but not CD4+ cells, from an immunized animal abrogated protection, confirming that E7-specific CTL are necessary and sufficient for TSA-specific protection in this model. Immunization with E7 and Algammulin (an alum-based adjuvant) induced a Th2-like response and provided no tumor protection. To investigate whether a Th2 T helper response to E7 could prevent the development of an E7-specific CTL-mediated protection, mice were simultaneously immunized with E7/Algammulin and GF001/Quil-A or, alternatively, were immunized with GF001/Quil-A 8 wk after immunization with E7/Algammulin. Tumor protection was observed in each case. We conclude that an established Th2 response to a TSA does not prevent the development of TSA-specific tumor protective CTL.
Fernando
G J
GJ
Center for Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia.
Stewart
T J
TJ
Tindle
R W
RW
Frazer
I H
IH
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D007110:Immunity, Active; D007444:Inulin / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments / Q000276:immunology; D062605:Quillaja Saponins; D012503:Saponins / Q000276:immunology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013945:Thymoma / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; C070342:Algammulin; D000534:Alum Compounds; D000951:Antigens, Neoplasm; D004338:Drug Combinations; D018984:Epitopes, T-Lymphocyte; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D062605:Quillaja Saponins; D012503:Saponins; C059731:oncogene protein E7, Human papillomavirus type 16; C046386:Quil A; D007444:Inulin