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-γ 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:.