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Immune synapses make a choice

The immunological synapse between T cells and the antigen-presenting dendritic cells acts as a locus for T cell activation. Now, Roberto Maldonado, Laurie Glimcher (Harvard School of Public Health, Boston, MA), and colleagues find that this synapse also helps the T cells decide between two different activated, differentiated fates based on the extent of colocalization of receptors at the synapse.

The end products of this decision are the bacteria-fighting Th1 cells and the parasite-fighting Th2 cells. Activation of the interferon- receptor (IFNGR) or interleukin 4 receptor (IL-4R) is known to favor Th1 production or Th2 production, respectively.

Now, Glimcher's group shows that the IFNGR but not IL-4R colocalizes with the T cell receptor (TCR) at the immunological synapse. The extent of this colocalization is greatest in mice that tend to generate more Th1 cells. IL-4, which favors production of Th2 cells, inhibits the colocalization.

Turning this colocalization correlation into causation will take more experiments. For example, cross-linking of the IFNGR and TCR might generate Th1 cells even in the Th2-favoring presence of IL-4. For now, the group points out that colocalization of the two receptors at the synapse puts the IFNGR near the source of its ligand and may set up a positive feedback between activation and differentiation pathways.

Reference:

Maldonado, R.A., et al. 2004. Nature. doi:10.1038/nature02916.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 530K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?