Yin-Yang T Cell Signaling

Science Signaling  20 Apr 2010:
Vol. 3, Issue 118, pp. ec121
DOI: 10.1126/scisignal.3118ec121

Immune responses are kept in check by CD4+ regulatory T cells (Treg) that suppress other immune cells, including CD4+ effector T cells (Teff). Treg and Teff cells have many signaling components in common, yet triggering through their T cell receptors (TCRs) leads to very different outcomes. Zanin-Zhorov et al. compared the recruitment of signaling molecules to the immunological synapse after TCR triggering in Treg and Teff cells. Although Treg cells do form synapses, signaling molecules that promote Teff activation, such as protein kinase C-θ (PKC-θ), were not recruited. Inhibition or depletion of PKC-θ in Treg cells led to suppressive activity against Teff cells, whereas costimulation enhanced PKC-θ recruitment and decreased suppression. Together, this suggests that PKC-θ is inflammatory in both Treg and Teff cells; however, by excluding it from the synapse, Treg cells are able to maintain suppression in the face of TCR signaling.

A. Zanin-Zhorov, Y. Ding, S. Kumari, M. Attur, K. L. Hippen, M. Brown, B. R. Blazar, S. B. Abramson, J. J. Lafaille, M. L. Dustin, Protein kinase C-θ mediates negative feedback on regulatory T cell function. Science 328, 372–376 (2010). [Abstract] [Full Text]