Gp120 reduces AHR and airway inflammation in a humanized mouse model of allergic asthma through activation of regulatory T cells

Abstract

Within this study we established a humanized mouse model of allergic asthma in immune deficient NOD-Scid gc–/– mice. For reconstitution of the animals we transferred 5 million peripheral blood mononuclear cells (PBMC) from allergic donors with sensitization against birch pollen intraperitoneally. The injection of PBMC together with birch and IL-4 followed by intranasal allergen challenge increased airway hyperresponsiveness (AHR) and airway inflammation after three weeks of engraftment. Recently it was shown that the HIV envelope protein gp120 functionally activates regulatory T cells (Tregs) through binding to the CD4 co-receptor that further leads to suppression of T effector cells (Blood 2009, 114 (6): 1263–69). To analyze the therapeutic effect of gp120 in our established humanized mouse model we treated the mice with gp120 on day 18. Administration of gp120 diminished AHR and influx of cells into the lung. To further analyze if Tregs are necessary for the occurring suppressive effects the CD25high expressing cells were removed from PBMC by depletion with dynabeads prior to engraftment. After depletion of Tregs treatment with gp120 no longer had any effect on airway inflammation in the humanized mouse model. These results confirm that gp120 promotes the tolerogenic function of Tregs and offer a new therapeutic strategy against atopic asthma.