The fabulous legacy of a Nobel Prize Laureate: Ralph M. Steinman, 1943-2011

摘要

The Nobel Prize in Physiology or Medecine 2011 was awarded to Ralph M. Steinman, Jules A. Hoffman and Bruce A. Beutler for the discovery of essential elements of innate immunity, in particular dendritic cells (DCs) and toll-like receptors (TLRs). Antigens become immunogenic and capable of triggering an adaptive immune response involving antigen-specific, MHC- restricted effector T cells, only if they are captured and presented by “accessory” cells. In 1972, Ralph M. Steinman and Zanvil Cohn identified in lymphoid tissues, cells with treelike, arborescent morphology that they named “dendritic cells” (DC) (from the greek word “tree” for tree, δένδρον) with a superior ability to induce alloreactive T cell proliferation in vitro (1978) and to stimulate the rejection of kidney allotransplants in rodents (1982). Thirty years after their discovery, DCare now known to play a seminal role in bridging innate and adaptive immunity, In addition DC are being used in numerous clinical studies all over the world to increase immunity to infectious or tumor-associated antigens. This effort involved the contribution of an international network of basicand clinical scientists spearheaded by Ralph M. Steinman to defineappropriate culture conditions to generate ex vivo DC from circulating or bone marrow precursors, to definefunctionally distinct DC subsets, to identifytheir maturation pathways including those relying on the stimulation of TLRs, and finally to develop DC based-vaccines to immunize patients infected with HIV or affected by cancer. Here, we will detail the history of DC and outline the therapeutic implications of Ralph M. Steinman’s seminal discovery.