DCs at the center of help: Origins and evolution of the three-cell-type hypothesis

This review traces the separate discoveries of dendritic cells, cross-priming, and help for cytotoxic T cell responses. The authors document the gradual convergence of these discoveries into the current models of cell-mediated immunity, spotlighting unanswered questions and future directions. Last year was the 10th anniversary of Ralph Steinman's Nobel Prize awarded for his discovery of dendritic cells (DCs), while next year brings the 50th anniversary of that discovery. Current models of anti-viral and anti-tumor immunity rest solidly on Steinman's discovery of DCs, but also rely on two seemingly unrelated phenomena, also reported in the mid-1970s: the discoveries of "help" for cytolytic T cell responses by Cantor and Boyse in 1974 and "cross-priming" by Bevan in 1976. Decades of subsequent work, controversy, and conceptual changes have gradually merged these three discoveries into current models of cell-mediated immunity against viruses and tumors.