Allergen exposure induces the activation of allergen‐specific Th2 cells in the airway mucosa of patients with allergic respiratory disorders

Abstract

Biopsy specimens were obtained from the bronchial or the nasal mucosa of three patients with grass pollen-induced bronchial asthma or rhinitis 48 h after positive bronchial or nasal provocation test with grass pollen extract. T cell clones (TCC), derived from these and control specimens, were then assessed for their phenotype, allergen-specificity, profile of cytokine secretion and ability to provide B cell help for IgE synthesis. Out of 50 and 61 CD4+ TCC derived from the bronchial mucosa of the two patient with atopic asthma 11 (22%) and 19 (31%), respectively, showed both proliferation and cytokine production in response to grass pollen allergens under major histocompatibility complex-restricted conditions. Of these 21 (70%) exhibited a clear-cut type 2 T helper (Th2) profile and induced IgE synthesis in autologous peripheral blood B cells in the presence of grass allergens. All the other 9 grass-specific clones showed a Th0 pattern of cytokine secretion, but only 1 provided moderate help for IgE synthesis. In contrast, the majority of TCC, derived under the same experimental conditions from the bronchial mucosa of two nonatopic patients with toluene diisocyanate-induced asthma, were CD8+ and most of them produced interferon-gamma or interferon-gamma and interleukin-5, but not interleukin-4, in response to nonspecific stimulation. Of 22 CD4+ TCC3 (14%) derived from the grass-stimulated mucosa of the patient with allergic rhinitis, but none of those derived from the unstimulated nostril of the same patient, exhibited proliferation and cytokine production in response to grass allergens. All had a clear-cut Th2 profile and provided help for IgE synthesis by autologous B cells. These data indicate that inhalation of the relevant allergen results in the activation of allergen-specific Th2 lymphocytes in the airway mucosa of patients with allergic respiratory disorders. These cells may play a central role in determining the nature of the inflammatory response in the airways of atopic patients.

Intervention of Thymus and Activation-Regulated Chemokine Attenuates the Development of Allergic Airway Inflammation and Hyperresponsiveness in Mice

“…There was a significant correlation between the number of CD4 ϩ cells in BAL fluids and the degree of AHR in asthmatic patients (34). Increasing evidence suggests that T lymphocytes, in particular CD4 ϩ T cells of the Th2 type, play an essential role in the development of the eosinophilic inflammatory response commonly found in asthma (35,36). Elevated IL-4, IL-5, and IL-13 levels in bronchial biopsies (36, 37), BAL cells, and blood (37) of allergic asthmatic patients have been reported, and therefore, it is suggested that these Th2-type cytokines play a key role in the eosinophil accumulation and resultant AHR found in asthmatics.…”

Increased circulating paternal antigen-specific IFN-γ- and IL-4-secreting cells during pregnancy in allergic and non-allergic women

“…Atopic disease is characterized by an individual predisposition to develop IgE mediated allergies against environmental allergens (Ishizaka and Ishizaka, 1971) and a Th2-polarized immunity (Del Prete et al, 1993). Atopic patients have an enhanced ability to produce IL-4, not only in response to allergens, but also to other antigens (Parronchi et al, 1992), and in line with this, atopic disease is associated with low IFN-γ secretion (Parronchi et al, 1991;Shimojo et al, 1996)).…”

Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones

“…IL-5-and IFN-g-positive cells have been identified in biopsies and bronchoalveolar lavage fluid (BALF) from asthmatic subjects [4]. In bronchial biopsies or BALF, after allergen challenge, many allergen-specific T cells are found which are of the Th2 phenotype [5,6], whereas in chronic asthmatic subjects, in whom cells have been recovered without allergen challenge, T cells are predominantly of the Th0 or Th1 phenotype [7].…”