August 6, 2012
Detailed below is a second achievement the Immune Tolerance Network (ITN) recently presented at the Member Society Symposium at the Federation of Clinical Immunology Societies (FOCiS) meeting, and how this work fits in with the broader pursuit of tolerance in autoimmunity.
Because of IL-2’s dual ability to promote both regulatory and inflammatory pathways, its use as a therapeutic in autoimmune indications is complex. Genetic and molecular studies have shown that defective IL-2 signaling in regulatory cells is a common feature in type I diabetes. Jane Buckner, MD (Benaroya Research Institute) reported on the ITN’s IL2-RAPA study that tested IL-2 combined with rapamycin in 10 type 1 diabetic subjects. Treated patients exhibited the anticipated increase in regulatory T cells confirming this cytokine's role in Teg development, previously demonstrated in preclinical models. Furthermore, the IL-2R signaling defect, which is present in these patients, was reversed for at least 1 year. However, these patients also developed a transient impairment in beta cell function following IL-2 therapy. Further analyses revealed that circulating eosinophils and natural killer cells were elevated in response to IL-2 administration, which may be the source of the observed clinical response. Two other recent studies demonstrated that low-dose IL-2 had clinical benefit in other autoimmune settings, underscoring the need to further refine IL-2 therapeutic approaches in a manner that accentuates its regulatory properties while minimizing potential inflammation.
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