A Role for T Helper-1 Cells in the Induction of Airway Hyperresponsiveness

Abstract

Jo/san Garssen, Ph.D.; F. P N kamp; H. Van Der Vliet; and H. Van Loveren I n a mouse model it was shown that T helper-i celldependent immune reactions directed against the small molecular weight compound, picryl chloride, induces increased airway resistance and airway hyperresponsiveness. Whether this is also true for low molecular weight compounds, such as toluene-diisocyanate, that induce asthmatic complaints in humans, in addition to T help-2 cell-dependent immune responses, remains to be clarified in future studies. Asthma may affect up to 10% of the population and remains yet underdiagnosed. One of the major efforts to subdivide asthma is based upon the absence or presence of allergy, ie, specffic IgE, in asthma patients. A major feature of asthma is an obstruction of the respiratory tract caused by the following: an increased smooth muscle tone, an increased thickness of airway walls, and an increased mucus secretion in the airways. Hyperresponsiveness, a major characteristic of asthma, is characterized as an enhanced response to a wide range of bronchoconstrictor stimuli. Knowledge of the mechanisms leading to hyperresponsiveness can provide insight into the pathogenesis of asthma and improve possibilities for therapy. Induction of bronchial hyperresponsiveness has often been thought to be correlated with the presence of airway inflammation and the capacity of the inflammatory cells to release certain types of inflammatory mediators.’ T cells are prominent in asthmatic airways and yet have received surprisingly little attention. T cells release mediators which can contribute to eosinophil activation2 and mast cell degranulation.’ Recently, Coffman et al proposed that there are at least 2 major subsets of T helper cells in mice, designed T help-i (Thi) and T help-2 (Th2) cells. Both subtypes can be distinguished by their cytokine profile. Cher and Mosmann5 showed that Thi cells are responsible for the classical delayed type hypersensitivity reaction (DTH). In contrast, Th2 cells are responsible for the regulation of immediate type I hypersensitivity reactions (IgE production, eosinophil activation). Research concerning mechanisms of the induction of asthmatic disorders is mainly focussed upon a possible role for Th2 cells. It is shown that expression of 11-5 mRNA in mononuclear cells infiltrating mucosal bronchial biopsies from patients with asthma, correlated with the presence of activated (CD25) CD4 T cells and activated eosinophils.6 In the blood of patients suffering from intrinsic asthma, no IgE antibodies to environmental antigens can be found. The precise mechanisms leading to airway obstruction in intrinsic asthma are still not known. Small molecular weight substances, such as isocyanates, to which antibodies are not