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Th2-type CD4+ cells neither enhance nor suppress antitumor CTL activity in a mouse tumor model.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1998 Sep 01; Vol. 161 (5), pp. 2421-7. - Publication Year :
- 1998
-
Abstract
- 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.
- Subjects :
- Adjuvants, Immunologic pharmacology
Alum Compounds
Amino Acid Sequence
Animals
Antigens, Neoplasm biosynthesis
Antigens, Neoplasm genetics
Antigens, Neoplasm immunology
CD8-Positive T-Lymphocytes immunology
Disease Models, Animal
Drug Combinations
Epitopes, T-Lymphocyte genetics
Epitopes, T-Lymphocyte immunology
Female
Immunity, Active
Inulin immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Nude
Molecular Sequence Data
Mutagenesis, Site-Directed
Oncogene Proteins, Viral biosynthesis
Oncogene Proteins, Viral genetics
Oncogene Proteins, Viral immunology
Papillomaviridae immunology
Papillomavirus E7 Proteins
Peptide Fragments immunology
Quillaja Saponins
Saponins immunology
Skin Neoplasms genetics
Skin Neoplasms immunology
Skin Neoplasms prevention & control
Thymoma genetics
Tumor Cells, Cultured
Cytotoxicity, Immunologic immunology
T-Lymphocytes, Cytotoxic immunology
Th2 Cells immunology
Thymoma immunology
Thymoma prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 161
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 9725239