T cell clone transfer model for steroid resistant asthma

Background: Glucocorticoid (GC) action on asthma has been partly explained by the inhibition of T cell activation. We analyzed the steroid sensitivity of ovalbumin (OVA) reactive helper T (Th) cell clones both in vitro and in vivo . Method: For in vitro experiments, Th clones were cultured with antigen presenting cells, OVA, and various concentrations of dexamethasone (DEX). The proliferative response of each Th clone was measured by 3 H-thymidine uptake. For in vivo experiments, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered with DEX subcutaneously. The number of infiltrating cells in bronchoalveolar lavage fluid (BALF) was measured. Results: Six Th clones were classified into steroid sensitive and steroid resistant clones in terms of the effects of GC on the proliferative responses analyzed in vitro . Airway infiltration of eosinophils and lymphocytes of mice transferred with steroid sensitive clones were effectively inhibited by the administration of DEX. In contrast, those of mice transferred with steroid resistant clones were not significantly inhibited by DEX, except that the number of eosinophils in the BALF of mice transferred with one steroid resistant clone, T5-1, was only partially reduced. Conclusion: Steroid sensitivity of Th clones measured in vitro were consistent with that of adoptively transferred asthma model measured in vivo . Steroid sensitive and resistant asthma models seem valuable for understanding the mechanisms of steroid resistance in severe asthma.