Correlation between eosinophilia induced by CD4+ T cells and bronchial hyper-responsiveness

Abstract

The relationship between CD4(+) T cell-mediated airway eosinophilic inflammation and bronchial hyper-responsiveness (BHR) was investigated. Ovalbumin-reactive T(h)0 clones were adoptively transferred to unprimed BALB/c mice and then the mice were challenged by inhalation of the relevant antigen. Upon antigen provocation, infused T(h) clones infiltrated into the airways, followed by the accumulation and degranulation of eosinophils, goblet cell hyperplasia, edema and increase in bronchial responsiveness to acetylcholine. Transfer of several clones that differed in the levels of IL-5 production revealed that the magnitude of in vivo eosinophilia strongly correlated with the IL-5-producing capacity of the infused T(h) clones. Administration of anti-IL-5 mAb almost completely suppressed antigen-induced eosinophilic inflammation and BHR. Administration of anti-IL-4 mAb or anti-IFN-gamma mAb enhanced the eosinophilia and BHR, whereas anti-IL-2 mAb did not affect them. The number of accumulated eosinophils significantly correlated with the intensity of BHR. Our present results clearly demonstrated that CD4(+) T cells induced BHR as a result of eosinophilic inflammation. IL-5 totally regulated both responses.

Dynamics of antigen-specific helper T cells at the initiation of airway eosinophilic inflammation

“…We have verified that allergic eosinophilic inflammation can be reconstituted by the adoptive transfer of antigenspecific Th2 clones into unprimed recipients [4,5]. Airway eosinophilic infiltration of T cell-transferred mice are dependent on IL-5 produced by the infused T cells.…”

“…Involvement of helper T cells in allergic eosinophilic inflammation has been demonstrated [4,5,8,12,20,21]. Activated CD4 + T cells that produce Th2 cytokines is increased in the bronchial mucosa of asthmatic patients [1,2,22,23].…”

“…Airway eosinophilic infiltration of T cell-transferred mice are dependent on IL-5 produced by the infused T cells. Moreover, the intensity of eosinophilic accumulation correlates well with that of the bronchial responsiveness to acetylcholine in vivo [5]. This system seems to be suitable for the analysis of trafficking of antigen-specific Th2 cells that initiate eosinophilic inflammation, as T cell clones are distinguishable from nonspecific "bystander" T cells.…”

Th2-Cell-Mediated Chemokine Synthesis Is Involved in Allergic Airway Inflammation in Mice

“…An immunoglobulin E/mast cell-dependent cascade has been implicated in allergic diseases [13], whereas our recent investigations clearly demonstrated that airway eosinophilic inflammation can be reconstituted in unprimed mice by the adoptive transfer of antigen-specific Th2 cells, independently of immunoglobulin E and mast cells [14, 15]. Antigen-induced lung eosinophilia in Th2-cell-transferred mice was dependent on IL-5 produced by the infused T cells [14].…”

“…Antigen-induced lung eosinophilia in Th2-cell-transferred mice was dependent on IL-5 produced by the infused T cells [14]. Furthermore, the number of accumulated eosinophils correlated well with bronchial responsiveness to nonspecific stimuli [15]. Therefore, this experimental system seems to be useful to analyze whether or how Th2 cells utilize chemokine/chemokine receptor interactions to induce eosinophilic inflammation.…”