Ruckert, R.R.RuckertBrandt, K.K.BrandtBraun, A.A.BraunHoymann, H.G.H.G.HoymannHerz, U.U.HerzBudagian, V.V.BudagianDurkop, H.H.DurkopRenz, H.H.RenzBulfone-Paus, S.S.Bulfone-Paus2023-10-252023-10-252005https://publica.fraunhofer.de/handle/publica/20790910.4049/jimmunol.174.9.55072-s2.0-17844369481IL-15 has been shown to accelerate and boost allergic sensitization in mice. Using a murine model of allergic sensitization to OVA, we present evidence that blocking endogenous IL-15 during the sensitization phase using a soluble IL-15Ralpha (sIL-15Ralpha) suppresses the induction of Ag-specific, Th2-differentiated T cells. This significantly reduces the production of OVA-specific IgE and IgG and prevents the induction of a pulmonary inflammation. Release of proinflammatory TNF-alpha, IL-1beta, IL-6, and IL-12 as well as that of Th2 cytokines IL-4, IL-5, and IL-13 into the bronchi are significantly reduced, resulting in suppressed recruitment of eosinophils and lymphocytes after allergen challenge. It is of clinical relevance that the airway hyper-responsiveness, a major symptom of human asthma bronchiale, is significantly reduced by sIL-15Ralpha treatment. Ex vivo analysis of the draining lymph nodes revealed reduced numbers of CD8, but not CD4, memory cells and the inability of T cells of sIL-15Ralpha-treated mice to proliferate and to produce Th2 cytokines after in vitro OVA restimulation. This phenomenon is not mediated by enhanced numbers of CD4(+)/CD25(+) T cells. These results show that IL-15 is important for the induction of allergen-specific, Th2-differentiated T cells and induction of allergic inflammation in vivo.enbronchial hyperreactivitygrowth inhibitorimmunological memoryinterleukin-15ovalbuminprotein subunitreceptor, Interleukin-2respiratory hypersensitivity615610620journal article