Dendritic Cell Scientist Wins Nobel Prize
Dendritic cell research got a boost this week when Ralph Steinman won the Nobel Prize for Physiology or Medicine. Sadly, Steinman did not live long enough to receive the Prize, he passed away just three days before the Nobel Prize was announced.
In 1973 Ralph Steinman and Zanvil Cohn published the first paper describing the discovery of dendritic cells in the Journal of Experimental Medicine. Cohn died in 1993 at the age of 66. In the paper Steinman and Cohn wrote, "morphological observations, both in vivo and in vitro, indicate that these novel cells can assume a variety of branching forms, and constantly extend and retract many fine cell processes. The term "dendritic" cell would thus be appropriate for this particular cell type." Since then, Steinman’s research was focused on this cell type.
A Dendritic Cell
Image Credit: FICKR AJC1
Initially dendritic cells were not given the due attention by immunologists. But research in this area of immunobiology gained momentum by early 1990s. Describing this "once neglected cell type," Jacques Banchereau and Ralph Steinman wrote in Nature, in 1998, "Dendritic cells in the periphery capture and process antigens, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. They (dendritic cells) not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions."
Dendritic cells are a rare subset of immune cells and are called professional antigen presenting cells. An antigen-presenting cell process antigens and display them in the folding of major histocompatibility complex (MHC) molecules on the cell surface. One of the major functions of dendritic cells is thus to take up antigenic materials, process and present the antigenic peptides to another subset of white blood cells called T cells. The presentation of an antigen by dendritic cell activates T cells even if they might not have encountered that antigen before (naive T cells).
Dendritic cells have the ability to initiate very strong immune responses. Therefore, dendritic cells play a very important role in infections and autoimmunity. These cells are present in virtually all tissues and are activated following "danger" signals.
The function of dendritic cells to activate killer T cells is used in the development of cancer immunotherapy. Dendritic cells treated with tumor antigens can present the tumor specific antigens on their surface MHC molecules and activate T cells. The activated T cells kill the tumor cells. According to The Scientist, “Steinman’s own life was extended using a dendritic cell-based immunotheraphy of his own design. But the immunologist finally lost his battle with pancreatic cancer last week.”
Dendritic cells are the sentinels of the immune system; their migration, maturation and mobilization are fundamental to immunity and tolerance. It is now known that dendritic cells are a heterogeneous group of cells that includes several distinct subpopulations. Whereas T cells are effector ‘soldiers’ of the immune system, dendritic cells can be called the ‘Generals’ that command and dictate to the T cells.
The award of 2011 Nobel Prize for Physiology or Medicine demonstrates the significance of this cell type in health and disease.
The 2011 Prize was divided, one half to Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity" and the other half jointly to Bruce A. Beutler and Jules A. Hoffmann "for their discoveries concerning the activation of innate immunity." Bruce Beutler was the first to isolate the cytokine tumor necrosis factor (TNF) and later developed the soluble TNF receptor, which is now marketed as Etanercept. Jules Hoffmann identified Toll receptors and their function in innate immune response. Hoffmann is the President of the French Academy of Sciences.
Sources used for this article:
Steinman RM, Cohn ZA (1973). "Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution". J. Exp. Med. 137 (5): 1142–62.
Banchereau J, Steinman RM (March 1998). "Dendritic cells and the control of immunity". Nature 392 (6673): 245–52.
Dendritic cells. Edited by Michael T. Lotze and Angus W. Thomson. Academic Press. San Diego, 1999.
Tracking the ‘General’: tagging skin-derived dendritic cells Trends in Biotechnology. Volume 22, Issue 2, February 2004, Pages 58-59.
Tumor antigen presentation by dendritic cells. Petersen TR, Dickgreber N, Hermans IF. Crit Rev Immunol. 2010;30(4):345-86.
Origin and development of dendritic cells. Liu K, Nussenzweig MC. Immunol Rev. 2010 Mar;234(1):45-54.