Depletion of CD56+CD3+ invariant natural killer T cells prevents allergen-induced inflammation in humanized mice.

Abstract Background CD56-expressing natural killer (NK) cells as well as invariant natural killer T (iNKT) cells have been shown to either promote or inhibit allergic immune responses. Objective The aim of the present study was to investigate the impact of these cells in a recently developed humanized mouse model of allergen-induced IgE-dependent gut and lung inflammation. Methods Nonobese diabetic-severe combined immunodeficiency-γc-/- mice were injected intraperitoneally with human PBMC or CD56-depleted (CD56neg) PBMC from highly sensitized birch or grass pollen allergic donors together with the respective allergen or with NaCl as control. Three weeks later, mice were challenged with the allergen rectally and gut inflammation was monitored by video mini-endoscopy and by histology. Furthermore, airway inflammation was measured after an additional intranasal allergen challenge. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org. Results Allergen-specific human IgE in mouse sera, only detectable after co-injection of the respective allergen, was reduced in mice being injected with CD56neg PBMC compared to mice receiving non-depleted PBMC. Consequently, allergen-induced IgE-dependent colitis, airway hyperreactivity and mucus-producing goblet cells were significantly inhibited in these mice. Interestingly, reconstitution of CD56neg PBMC with non-depleted CD56+ cells and with CD56+CD3+ iNKT cells restored gut as well as lung inflammation while addition of CD3-depleted CD56+ cells did not. Conclusion These results demonstrate that allergen-specific gut and lung inflammation in PBMC-engrafted humanized mice is promoted by CD56+CD3+ iNKT cells which opens new possibilities of therapeutic intervention in allergic diseases.