Contrary to what was previously thought, the maturation state of dendritic cells is not what determines whether the immune system's killer T cells are activated or not. In the November issue of Nature Immunology, scientists from the Rockefeller University, New York show that mature DCs depend on the presence of CD4 T cells, to activate, rather than shut down, CD8 killer T cells.
This is a critical distinction. The immune system must discriminate between the self proteins and pathogenic infectious agents. A reaction to the former initiates the tissue destruction known as autoimmunity. Fortunately, most autoreactive CD8 T cells are eliminated in the thymus, but some do escape. These potentially self-destructive CD8 T cells can be tolerized (that is, made unresponsive, or tolerant, to its specific antigen) by interactions with dendritic cells. Immature dendritic cells take up proteins, which they then take with them to the lymph nodes, maturing in the process. In the nodes the mature dendritic cells encounter CD8 T cells, which are then either activated or tolerized, depending on whether the protein is foreign or self.
The old paradigm to explain how dendritic cells can both tolerize and activate CD8 T cells depended upon the stage of dendritic cell development, because immature DCs could only deliver one signal (which results in tolerance) to the CD8 T cell, whereas mature DCs can deliver two. Albert and colleagues suggest a new model: the critical checkpoint is not dendritic cell maturation, but instead the presence of a third signal, which is provided by CD4 T cells.
Matthew L. Albert
Laboratory of Neuro-Immunology, Rockefeller University, New York, USA
Tel: +1 212 327 7451
Additional contact for comment on paper:
Immunology Division, Walter and Eliza Hall Institute of Medical Research
Tel: +61 393 452 531
(C) Nature Immunology press release.
Message posted by: Trevor M. D'Souza
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