Methods: BALB/c mice were sensitized by injection of 100 μg of ovalbumin (OVA) with 2 mg of alum adjuvant on days 0 and 14. On days 22, 24, 26, and 28, the mice inhaled aerosolized 1% OVA in PBS. Some groups of mice were treated with 300 μg of anti-CD70 mAb or control rat IgG in the induction or effector phase. Airway hyperresponsiveness was measured by methacholine-induced airflow obstruction. Bronchoalveolar lavage fluid was collected and differential cell count was performed.
Results: Administration of anti-CD70 mAb during the induction phase, but not the effector phase, reduced airway hyperreactivity with a concomitant decrease of eosinophil infiltration in the lung as compared with control IgG-treated mice. Treatment with anti-CD70 mAb also resulted in decreased production of Th2 cytokines (IL-4, IL-5, and IL-13) in the bronchoalveolar lavage fluid and draining lymph node cell cultures. Notably, OVA-specific CD4 T cells were clearly separated into two populations by CD27 expression, CD27+ or CD27-, in the lymph node from OVA-immunized DO11.10/Rag-2-/- mice. The CD27+ CD4 T cells produced a high level of IFN-γ. In contrast, CD27- CD4 T cells produced high levels of IL-4, IL-5, and IL-13. These results suggest that the CD27- CD4 T cell population represents effector Th2 cells. Moreover, the population of CD27- CD4 Th2 cells was significantly reduced by the anti-CD70 mAb treatment.
Conclusions: A potent inhibition of the inflammatory response in mouse model of asthma was achieved with anti-CD70 mAb administration. CD70-CD27 interaction appears to play a critical role in the development of pathogenic Th2 cells.