Induction of T helper type 1–like regulatory cells that express Foxp3 and protect against airway hyper-reactivity

Speaker: 曾昭穎                    Time: 15:10~16:00  03/23/2005

Commentator: 林以行 老師          Place: Room 601

Abstract:

   Asthma is a respiratory disorder characterized by airway hyperreactivity (AHR) and inflammation and is associated with high serum IgE and overproduction of IL-4, IL-5, and IL-13 by allergen-specific Th2 cells. Previous studies by this same authors demonstrated that heat-killed Listeria monocytogenes (HKL) plus OVA in immunotherapy successfully reversed ongoing Ag-specific Th2-dominated responses toward Th1-dominated responses. The inhibitory effect on AHR depended on the presence of IL-12 and on CD8⁺ T cells in the murine model. Previously, Th1 cells secreting interferon- γ (IFN-γ) ) are thought to be critically involved in downmodulating Th2-driven airway hyperreactivity and asthma. However, IFN-γ secreting Th1 cells exacerbated pulmonary inflammation rather than counterbalanced the effects of Th2 cells (1). These suggests that other cell types, for example, interleukin-10 (IL-10) or transforming growth factor-b (TGF-b))  secreting cells, might be more effective in relieving airway inflammation in asthma. In past finding that following respiratory exposure to allergen, regulatory T (T_R) cells were developed, which produced high levels of IL-10 (2). In this article, the authors find a unknown adaptive T_R cell type that expresses IFN-, T-bet, IL-10 and Foxp3 and has a potent inhibitory function. The T_H1-related T_R cells were induced by CD8⁺ DCs and expressed T-bet, these T_R cells are related to but are distinct from T_H1 cells (3).

References:

1.      Hansen G, et al. Vaccination with Heat-Killed Listeria as Adjuvant Reverses Established Allergen-Induced Airway Hyperreactivity and Inflammation: Role of CD8⁺ T Cells and IL-18. The Journal of Immunology, 164: 223-230, 2000

2.      Akbari, O, et al. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat. Med. 8, 1024–1032 , 2002

3.      Stock P, et al. Induction of T helper type 1–like regulatory cells that express Foxp3 and protect against airway hyper-reactivity. Nature Immunology 5, 1149 – 1156 , 2004