Comparative Analysis of Steroid Sensitivity of T Helper Cells in vitro and in vivo

Abstract

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 ³H-thymidine uptake. For in vivo experiments, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered DEX subcutaneously. The number of infiltrating cells in bronchoalveolar lavage fluid (BALF) was measured. Results: Six Th clones were classified as steroid-sensitive or steroid-resistant clones in terms of the effects of GC on the proliferative responses analyzedin 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; the number of eosinophils in the BALF of mice transferred with 1 steroid-resistant clone, i.e. T5-1, was only partially reduced. Conclusion: The steroid sensitivity of Th clones measured in vitro was consistent with that of an adoptively transferred asthma model measuredin vivo. Steroid-sensitive and resistant asthma models seem valuable for understanding the mechanisms of steroid resistance in severe asthma.