Editors' ChoiceTCR Signaling

Vitamin Stimulant

Science Signaling  23 Mar 2010:
Vol. 3, Issue 114, pp. ec87
DOI: 10.1126/scisignal.3114ec87

Antigen-primed T cells are more responsive to stimulation of the T cell antigen receptor (TCR) than are naïve cells; they produce increased amounts of cytokines and exhibit increased mobilization of intracellular Ca2+. To characterize how responsiveness is increased during differentiation from naïve cells to primed cells, von Essen et al. compared the responses of untreated naïve human T cells to those of naïve cells that had been stimulated with antibodies against CD3 and CD28 and then allowed to rest. Upon restimulation, activation of the TCR-associated molecules Lat and Zap70 was greater in naïve cells than in primed cells; however, activation of extracellular signal–regulated kinase was greater in the primed cells, which suggested defective phospholipase γ1 (PLC-γ1) activation in naïve cells. Western and Northern blotting assays showed that PLC-γ1 mRNA and protein were more abundant in primed cells than in naïve cells, and this increase was driven by stimulation of the naïve cells. Increases in PLC-γ1 abundance were preceded by increases in the abundance of the vitamin D receptor (VDR), and VDR antagonists blocked TCR-dependent increases in PLC-γ1 abundance in naïve T cells. T cells from patients with low concentrations of serum vitamin D were less responsive to TCR stimulation than were T cells from healthy controls. The TCR-stimulated increase in expression of the gene encoding VDR was dependent on activation of p38 mitogen-activated protein kinase (MAPK); inhibition of p38 MAPK also blocked increases in the abundance of PLC-γ1. Together, these data suggest that initial activation of alternative TCR signaling, through p38 MAPK, enables VDR-dependent increased production of PLC-γ1, which increases the responsiveness of primed T cells to TCR stimulation.

M. R. von Essen, M. Kongsbak, P. Schjerling, K. Olgaard, N. Ødum, C. Geisler, Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat. Immunol. 11, 344–349 (2010). [PubMed]

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