Inducible costimulator-positive T cells are required for allergen-induced local B-cell infiltration and antigen-specific IgE production in lung tissue

BACKGROUND: Airway inflammation plays a critical role in the pathogenesis of asthma. In susceptible individuals, airway allergen exposure results in the recruitment of inflammatory cells into lung tissue, leading to a local inflammatory response. Central to the induction and regulation of this process are T lymphocytes. OBJECTIVE: Blocking of the newly discovered costimulatory T-cell molecule inducible costimulator (ICOS) with monoclonal antibodies was shown to ameliorate allergic airway inflammation in models of murine asthma. Although these observations indirectly support an association between ICOS and the development of allergic inflammation, the role of the ICOS + T cell in the pathogenesis of allergic airway disease remains unclear. METHODS: We used an adoptive transfer model to analyze further the role of antigen-specific ICOS + T cells during the effector phase of allergic airway inflammation. In vitro stimulated CD4 + T cells from mice transgenic for an ovalbumin-specific T-cell receptor (DO11.10) were sorted into ICOS-enriched and ICOS-depleted T-cell fractions and transferred into BALB/c recipient mice. RESULTS: Transfer of the ICOS-enriched T-cell population followed by allergen airway challenges induced pronounced infiltration of recipient T and B cells and local production of allergen-specific IgE by intrapulmonary plasma cells. In contrast, transfer of the ICOS-depleted T-cell fraction resulted in the recruitment of significantly lower numbers of B cells and no local IgE production. CONCLUSION: These data indicate that expression of ICOS defines a subset of T effector cells that are required for B-cell infiltration and local IgE production in lung tissues on allergen airway exposure.