Immune deficiencies, infection, and systemic immune disordersIL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis
Section snippets
Patients
Diagnostic data were obtained from patients with FHL/MAS during routine clinical care at UZ Leuven. Neonatal patients were excluded from analysis. Of the 7 patients identified during active FHL/MAS, 3 had not received any treatment related to an FHL/MAS episode at the time of the analysis, whereas 4 other patients had already started corticosteroids, cyclosporine treatment, or both. Written informed consent was obtained from each patient. The Ethics Committee of the University of Leuven and
Defective Treg cell homeostasis during HLH
To determine the proximal cause of uncontrolled inflammation in patients with FHL, we investigated the properties of Treg cells, one of the key regulators of immune activation. Perforin knockout (Prf1−/−) mice, with the same underlining genetic deficiency as patients with FHL, were used to assess Treg cell status. To investigate Treg cell homeostasis during inflammation in an FHL murine model, wild-type and Prf1−/− mice were treated with LCMV (Armstrong strain). After infection, wild-type mice
Discussion
In this report we describe the fate of Treg cells under the debilitating condition of LCMV-induced FHL. We demonstrated that after excessive activation of CD8+ T cells, IL-2 production is reduced and the consumption hierarchy is reversed, leading to preferential consumption by inflammatory CD8+ T cells to the detriment of anti-inflammatory Treg cells.
Under physiologic conditions, Treg cells are important actors in peripheral immune tolerance, creating a buffer against spontaneous immune
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Supported by the VIB, ERC (-IMMUNO), FWO (G051912N) and IUAP (T-TIME). S.H.-B. and B.C. were supported by FWO postdoctoral fellowships.
Disclosure of potential conflict of interest: S. Humblet-Baron receives research funding from FWO. J. Dooley receives research funding from FWO. B. Cauwe is an employee of ABBVIE as a Medical Science Liaison. F. Baron received payments from Genzyme and received travel support from Celgene, Genzyme, and Novartis. A. Liston receives research funding FWO and ERC. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.