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Sci Rep. 2018 Oct 31.

The PDL1-inducible GTPase Arl4d controls T effector function by limiting IL-2 production.

Tolksdorf F, Mikulec J, Geers B, Endig J, Sprezyna P, Heukamp LC, Knolle PA, Kolanus W, Diehl L

Interleukin-2 (IL-2) is a key regulator of adaptive immune responses but its regulation is incompletely understood. We previously found that PDL1-dependent signals were pivotal for liver sinusoidal endothelial cell-mediated priming of CD8 T cells, which have a strongly reduced capacity to produce IL-2. Here, we show that the expression of the ARF-like GTPase Arl4d is PD-L1-dependently induced in such LSEC-primed T cells, and is associated with reduced IL-2 secretion and Akt phosphorylation. Conversely, Arl4d-deficient T cells overproduced IL-2 upon stimulation. Arl4d-deficiency in CD8 T cells also enhanced their expansion and effector function during viral infection in vivo. Consistent with their increased IL-2 production, Arl4d-deficient T cells showed enhanced development into KLRG1CD127 short-lived effector cells (SLEC), which is dependent on IL-2 availability. Thus, our data reveal a PD-L1-dependent regulatory circuitry that involves the induction of Arl4d for limiting IL-2 production in T cells.

PMID: 30382149