RATIONALE: Novel strategies for dendritic cell (DC) modulation of T cells and B cells could improve allergen immunotherapy. We investigated whether human IgM antibody, B7-DCXAb, which binds to B7-DC and enhances DCs' antigen uptake and retention, migration, and cytokine production, improves the efficacy of immunotherapy.METHODS: Mice were sensitized by intraperitoneal injection of OVA or house dust mite (HDM) antigens plus alum and then treated by intravenous B7-DCXAb injection plus subcutaneous, intranasal or sublingual administration of antigen. The efficacy was evaluated by antigen-specific antibodies, splenocyte recall responses, and airway inflammatory responses to intranasal antigen challenge.RESULTS: OVA-sensitized mice developed anti-OVA IgE and IgG1, Th2-type splenocyte responses to OVA and airway eosinophilic inflammation after OVA challenge. When these mice were treated by intravenous B7-DCXAb plus intranasal OVA, anti-OVA IgE and IgG1 decreased by 75∼95% within 1 week; this decrease persisted for >8 weeks. Anti-OVA IgG2a decreased transiently. Splenocyte production of IL-4, IL-5, and IL-13 in response to OVA was abolished; no increases in IFN-g or IL-17 were noted. In OVA-challenged mice, airway eosinophilia and lung levels of IL-4, IL-5 and IL-13 were reduced by >90%. Immunotherapeutic effects were also observed with intravenous B7-DCXAb plus sublingual OVA, but not with intravenous B7-DCXAb plus subcutaneous OVA or with intravenous B7-DCXAb alone. Furthermore, HDM-sensitized mice were treated successfully by intravenous B7-DCXAb plus intranasal HDM.CONCLUSIONS: B7-DCXAb injection plus mucosal administration of antigen effectively treats both T cell and B cell allergic responses. Manipulation of DCs may enhance the efficacy of allergen immunotherapy. RATIONALE: Novel strategies for dendritic cell (DC) modulation of T cells and B cells could improve allergen immunotherapy. We investigated whether human IgM antibody, B7-DCXAb, which binds to B7-DC and enhances DCs' antigen uptake and retention, migration, and cytokine production, improves the efficacy of immunotherapy. METHODS: Mice were sensitized by intraperitoneal injection of OVA or house dust mite (HDM) antigens plus alum and then treated by intravenous B7-DCXAb injection plus subcutaneous, intranasal or sublingual administration of antigen. The efficacy was evaluated by antigen-specific antibodies, splenocyte recall responses, and airway inflammatory responses to intranasal antigen challenge. RESULTS: OVA-sensitized mice developed anti-OVA IgE and IgG1, Th2-type splenocyte responses to OVA and airway eosinophilic inflammation after OVA challenge. When these mice were treated by intravenous B7-DCXAb plus intranasal OVA, anti-OVA IgE and IgG1 decreased by 75∼95% within 1 week; this decrease persisted for >8 weeks. Anti-OVA IgG2a decreased transiently. Splenocyte production of IL-4, IL-5, and IL-13 in response to OVA was abolished; no increases in IFN-g or IL-17 were noted. In OVA-challenged mice, airway eosinophilia and lung levels of IL-4, IL-5 and IL-13 were reduced by >90%. Immunotherapeutic effects were also observed with intravenous B7-DCXAb plus sublingual OVA, but not with intravenous B7-DCXAb plus subcutaneous OVA or with intravenous B7-DCXAb alone. Furthermore, HDM-sensitized mice were treated successfully by intravenous B7-DCXAb plus intranasal HDM. CONCLUSIONS: B7-DCXAb injection plus mucosal administration of antigen effectively treats both T cell and B cell allergic responses. Manipulation of DCs may enhance the efficacy of allergen immunotherapy.