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Mechanisms of tolerance and Th2 cell activation in asthma
  1. R Baghai-Ravary
  1. Specialist Registrar in Respiratory Medicine, Homerton University Hospital, London, UK;

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Multiple factors are involved in the correct regulation of an immune response to common antigens. Two studies using asthma models in mice provide an insight into the immunological mechanisms of T helper 2 (Th2) cell activation in atopic asthma.

There are two subsets of human and mouse dentritic cells (DC): the myeloid (mDC) and plasmacytoid (pDC) types. de Heer et al show that inhaled antigen is taken up and presented to draining nodal T cells in the lung by both DCs. On selective depletion of pDCs, inhalation of a normally inert antigen induces Th2 cell activation and effector cytokine release (IL-5, IL-10, IL-13, interferon γ), goblet cell hyperplasia, eosinophilic airway inflammation, and specific serum IgE production. However, the adoptive transfer of antigen exposed pDC in mice before subjecting them to an immunogenic asthma protocol led to tolerance through inhibition of mDC induced generation of Th2 cells. Atopic asthma may be caused by pDC dysfunction, but this hypothesis remains to be proven before treatments aimed at potentiating pDC activity can be considered.

Ostroukhava et al show that FOXP3, a transcription factor, is only present on the surface of CD4+ T cells in which tolerance has been induced by repeated exposure to a low dose inhaled antigen. The administration of CD4+ T cells bearing cell surface TGF-β to naïve mice is shown to induce tolerance to subsequent antigen exposure. In addition, the depletion of TGF-β+ cells before antigen exposure resulted in proliferation of TGF-β cells and Th2 mediated allergic phenotype. The authors suggest that early antigen exposure could induce tolerance to commonly inhaled antigens in those at risk of allergic disease. However, important questions remain about the inhibitory pathways through which TGF-β+ cells induce tolerance, the role of FOXP3, antigen dosing and specificity, and defining the population predisposed to atopy.

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