New study provides insight into Hemophagocytic Lymphohistiocytosis
Thursday, March 10, 2016 at 11:52AM Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory disease caused by macrophage activation. Watch "Max the Angry Macrophage":
In patients with the primary (genetic) form of the disease, the underlying cause of illness is a defect in CD8 T cells which makes them inefficient at clearing viruses. The connection between this defect and the disease onset has, however, been unclear.In a new study from the Translational Immunology laboratory, we used a mouse model of HLH to dissect the mechanism leading to disease. We found that the CD8 T cells try to overcome their defect in anti-viral killing by becoming more and more activated. One consequence of this activity is that they start consuming a key cytokine in the blood, IL-2. IL-2 is necessary for the survival of regulatory T cells, the key cell type for calming down a hyper-active immune system. When the activated CD8 T cells consumed all of the IL-2, the regulatory T cells started dying off due to IL-2 starvation, leading to excessive inflammation. The same lack of regulatory T cells was found in HLH patients, indicating that this is the mechanism driving inflammatory disease in patients. These results identify a new therapeutic target for HLH patients.
Humblet-Baron S, Franckaert D, Dooley J, Bornschein S, Cauwe B, Schönefeldt S, Bossuyt X, Matthys P, Baron F, Wouters C, Liston A. 'IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis.' J Allergy Clin Immunol. 2016 Mar 3. pii: S0091-6749(16)00115-9. doi: 10.1016/j.jaci.2015.12.1314.
Liston lab, Medicine, immunology
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