Successful transfer of late phase eosinophil infiltration in the lung by infusion of helper T cell clones.

Abstract

Bronchial asthma is characterized by chronic eosinophilic inflammation of the bronchial mucosa. Accumulating evidences suggest that activated T cells and T cell cytokines play critical roles in the local accumulation and activation of eosinophils. To further delineate the critical role of T cells on asthma, we tested the possibility whether eosinophilic inflammation of the bronchial mucosa is induced by transferred T cell clones, in the absence of antigen-specific immunoglobulins (IgE, A, and G). Ovalbumin-specific Th2 clones were established and cytokine profiles were determined. Eosinophilic inflammation accompanied with airway hyperresponsiveness occurred only when unprimed mice were transferred with IL-5 producing Th2 clones and challenged by the inhalation of relevant antigen. Increase of IL-5 concentration in bronchoalveolar lavage fluid (BALF) was detected after the challenge, indicating the local production of cytokines by the transferred T cells, and preceded the appearance of the airway eosinophilia. Eosinophil infiltration was completely suppressed by the administration of anti-IL-5 neutralizing antibody, indicating the essential role of IL-5 in this model. The intensity of the eosinophil accumulation in vivo correlated well with the capacity of the T cell clones to produce IL-5 in vitro. We concluded that the existence of IL-5-producing helper T cells is sufficient for the development of the eosinophilic inflammation at the bronchial mucosa upon inhalation challenge of the relevant antigen.

Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation

“…Adoptive transfer of allergen-specific Th2 cells has also been shown to promote airway eosinophilia, mucus production, and hyperreactivity (28)(29)(30). The role of Th1 cells is less clear.…”

Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice

“…In a murine asthma model in which mice were sensitised to chicken ovalbumin (OVA) and then challenged with aerosolised OVA, the phenotype is also considered to be Th2 dominant because of Th2 pattern of cytokines in the BALF and cytokines produced by T-cells from lung lymph nodes and spleen cells. Furthermore, adoptive transfers of Th2 clones or of the polarised Th2 population into naive mice followed by transbronchial antigen challenge induced an asthma-like phenotype in the lung [3,4]. Therefore, induction or the adoptive transfer of Th1 cells may be a possible therapeutic strategy for asthma, since Th1 cells can antagonise the Th2-driven mechanisms.…”

CD4+ T-Lymphocytes Regulate Airway Remodeling and Hyper-Reactivity in a Mouse Model of Chronic Asthma

“…Mice lacking CD4 ϩ T cells because of deficient ability to express class II major histocompatibility complex antigens fail to develop eosinophil-dominated inflammation or AHR following exposure to antigen (Brusselle et al, 1994). Adoptive transfer of CD4 ϩ T cells from sensitized mice is associated with recruitment of eosinophils and the development of AHR following antigen challenge (Hogan et al, 1998a;Kaminuma et al, 1997). Conversely, depletion of CD4 ϩ T-lymphocytes by administration of antibody abrogates AHR (Gavett et al, 1994;Hogan et al, 1998b;Mould et al, 2000).…”