Supraphysiological levels of IL-15 accelerate immune reconstitution in lymphopenic mice (134.16)

Abstract

Abstract Loss of lymphocytes and T cells are a significant medical problem in AIDS and other immunodeficiencies, as well as after various treatments and cytoreductive therapies. T cell recovery after lymphopenia is delayed and incomplete and this can lead to prolonged immune dysfunctions. Lymphoablated patients have rapid and transient increases of circulating homeostatic cytokines IL-7 and IL-15, suggesting a role for these factors in immune reconstitution. Analysis of sera from lymphoablated patients revealed that the main form of circulating IL-15 is in a complex with soluble IL-15Rα (IL-15sRα). We have shown that injection of DNA expressing supraphysiological levels of IL-15/IL-15sRα in normal mice led to dose-dependent increases in the number and frequency of NK and T cells. The effect of IL-15/IL-15sRα on immune reconstitution was tested in mice lymphodepleted by cyclophosphamide (CTX) treatment. A single administration of IL-15/IL-15sRα DNA accelerates the full recovery of NK cells in spleen and lung. Two administrations of IL-15/IL-15sRα DNA promote the recovery of T cells in spleen within 14 days, faster than CTX-treated mice (p=0.017 Wilcoxon). T and NK cells from mice treated with supraphysiological levels of IL-15/IL-15sRα show greater degranulation and IFN-γ production after in vitro stimulation. These results suggest that IL-15 can contribute to rapid immune reconstitution, and suggest the use of IL-15/IL-15sRα to accelerate recovery from lymphopenia.