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Sci Rep. 2018 Oct 31;8(1):16123. doi: 10.1038/s41598-018-34522-4.

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

Author information

1
LIMES (Life and Medical Sciences Institute), Molecular Immunology, University of Bonn, Bonn, Germany.
2
Institute of Molecular Medicine, University Hospital Bonn, Bonn, Germany.
3
Division of Virus-Associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
5
Institute of Pathology, University of Cologne, Cologne, Germany.
6
Institute of Molecular Immunology and Experimental Oncology, Technical University Munich, Munich, Germany.
7
Institute of Molecular Medicine, University Hospital Bonn, Bonn, Germany. li.diehl@uke.de.
8
Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. li.diehl@uke.de.

Abstract

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 KLRG1+CD127- 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.

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