Dendritic cells purified from myeloma are primed with tumor-specific antigen (idiotype) and activate CD4+ T cells

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FONTE

The National Academy of Sciences

RESUMO

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.

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