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T-cell responses

Showing cytokines the way out

Nature Reviews Immunology volume 6, page 167 (2006)Cite this article

In this study, Huse et al. show, using intracellular cytokine staining, that the secretion of interleukin-2 (IL-2) and interferon-γ (IFNγ), as well as IL-3 and IL-10, is focused at the immunological synapse in activated TH cells. By contrast, tumour-necrosis factor (TNF) was shown to be focused at the immunological synapse briefly, but as the response developed, TNF became scattered throughout the cell. Using video microscopy, TNF secretion by live TH cells was shown to be distributed throughout the cells, with a bias away from the immunological synapse over time. The intracellular distribution of CC-chemokine ligand 3 (CCL3) and CCL5 was similar to TNF, although with delayed kinetics. In addition, the TH2-cell-associated cytokine IL-4 was found to be distributed throughout the cell.

But how does the cell coordinate the movement of certain cytokines in one direction while sending others on a different route? This study shows that specific trafficking proteins co-localize with certain cytokines at these different locations. RAB3D and RAB19, members of the RAB family of small GTPases — which associate with different intracellular compartments — were found to localize with IL-2 and IFNγ at the synapse, whereas the SNARE (soluble N-ethylmaleimide-sensitive accessory-protein receptor) protein, syntaxin 6, localized with TNF throughout the cell, indicating the use of distinct processes for directional cytokine release.

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ORIGINAL RESEARCH PAPER

  1. Huse, M., Lillemeier, B. F., Kuhns, M. S., Chen, D. S. & Davis, M. M. T cells use two directionally distinct pathways for cytokine secretion. Nature Immunol. 29 Jan 2006 (10.1038/ni1304)

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Authors
  1. Olive Leavy
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Leavy, O. Showing cytokines the way out. Nat Rev Immunol 6, 167 (2006). https://doi.org/10.1038/nri1811

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