Blocking IL-15 prevents the induction of allergen-specific T cells and allergic inflammation in vivo.
IL-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.
Rückert
René
R
Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany.
Brandt
Katja
K
Braun
Armin
A
Hoymann
Heinz-Gerd
HG
Herz
Udo
U
Budagian
Vadim
V
Dürkop
Horst
H
Renz
Harald
H
Bulfone-Paus
Silvia
S
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006131:Growth Inhibitors / Q000502:physiology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D019409:Interleukin-15 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000037:antagonists & inhibitors / Q000276:immunology; D021122:Protein Subunits / Q000502:physiology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D000485:Allergens; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D007073:Immunoglobulin E; D010047:Ovalbumin