Dendritic cells purified from myeloma are primed with tumor-specific antigen (idiotype) and activate CD4+ T cells.
Multiple myelomas produce tumor-specific antigen (TSA) in the form of idiotype (Id) on monoclonal Ig. CD4(+) T cells can recognize Id-peptide on MHC class II molecules and protect against challenges with MOPC315 cells, which are, as common for myelomas, class II-negative. The present study explains these previous results by demonstrating that Id can be transferred from myeloma cells to antigen-presenting cells (APC), which present processed Id-peptide on their class II molecules to Id-specific T cell receptor-transgenic (TCR-TG) CD4(+) T cells. Id-primed tumor APC were heterogeneous, the majority being dendritic cells with class II(+), CD11b(+) CD11c(+) CD40(+) CD80(+) CD86(+) markers. The APC were localized beneath CD31(+) endothelial cells of tumor microvessels, and their frequency declined with tumor progression. The APC could stimulate Id-specific naive TCR-TG, short-term polarized TCR-TG, and cloned CD4(+) T cells to proliferate and produce cytokines in vitro. Furthermore, small MOPC315 tumors established in Id-specific TCR-TG mice contained clusters of activated (CD69(+)CD25(+)) and proliferating (BrdUrd(+)) Id-specific transgenic CD4(+) blasts. The activated Id-specific T cells were located adjacent to Id-primed dendritic cells in the tumor. Thus, a TSA can be transferred in vivo from myeloma, and possibly other types of cancer cells to APC for MHC class II presentation to CD4(+) T cells.
Dembic
Z
Z
Institute of Immunology and the Department of Oral Biology, University of Oslo, The National Hospital, 0027 Oslo, Norway. zlatko.dembic@labmed.uio.no
Schenck
K
K
Bogen
B
B
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007130:Immunoglobulin Idiotypes; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology*; D009368:Neoplasm Transplantation; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes; D011948:Receptors, Antigen, T-Cell