Characteristics of a potent tumor vaccine-induced secondary anti-tumor T cell response.
This study describes a tumor vaccine-induced secondary in vivo T cell response to an immunodominant epitope of beta-galactosidase (Gal) as a model tumor-associated antigen. DBA/2 mice are primed with lacZ transfected live ESbL tumor cells (ESbL-Gal) in the ear pinna, a site which had previously been shown to be non-tumorigenic and immunogenic. Intraperitoneal challenge of such mice with tumor vaccine (i.e., 10(7) irradiation-inactivated ESbL-Gal cells) leads to the production of a powerful CD8+ CTL response and to the establishment of immune memory. Using peptide/MHC-tetrameric complexes, clonal expansion of antigen-specific T cells could be detected during the primary response in bone marrow (BM) and during the secondary response in the peritoneal cavity and BM. The secondary response in the peritoneal cavity involved a >80-fold enrichment of epitope specific CD8+ T cells and the release of various cytokines, including IL-12 and TNF-alpha. The recruitment and/or expansion of Gal specific T cells within the peritoneal cavity could be inhibited by anti-IL-12 and anti-TNF-alpha monoclonal antibody (mAb) treatment. Interestingly, the secondary CTL response was inhibited by anti-IL-12 but not by anti-TNF-alpha mAb. The results characterize a strong systemic CD8+ memory T cell response to a cell bound antigen without the use of adjuvant.
Mahnke
Yolanda D
YD
German Cancer Research Center, Division of Cellular Immunology, D-69120 Heidelberg, Germany.
Schirrmacher
Volker
V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001853:Bone Marrow / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D007156:Immunologic Memory; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000276:immunology; D007763:Lac Operon / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000628:therapy*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010529:Peritoneal Cavity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014611:Vaccination; D001616:beta-Galactosidase / Q000276:immunology
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D001616:beta-Galactosidase