Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial T-H2 response to a T-H1 response in situ: An immunocytochemical study

In the pathogenesis of atopic dermatitis (AD), IgE plays an important role; and T-H2 cells. producing IL-4, have been ascribed a key role in allergic diseases such as AD. To investigate the role of T-H subpopulations in the onset and continuation of AD, we performed atopy patch tests (APTs) with house dust mite allergen in patients with AD. Punch biopsy specimens were taken from the APT site, and sections were immunocytochemically double-stained for IL-4 and interferon-gamma together with different membrane markers. This provides a unique model for studying the kinetics of the TH0, T-H1, and T-H2 responses in situ. The results show that in lesional skin interferon-gamma-positive cells predominate over IL-4-positive cells. The interferon-gamma-positive cells are mainly CD3(+) and, in particular, CD4(+) cells; the remainder are CD8(+), RFD-1(+), and RFD-7(+) cells. The IL-4-positive cells are exclusively CD4(+) T cells; no eosinophils or mast cells were found to stain for IL-4. With regard to the T-H cell response, a clear dichotomy of the eczematous response to allergen in skin was observed. In the initiation phase IL-4 production by T-H2 and T-H0 cells is predominmant over interferon-gamma production by T-H1 and T-H0 cells. In the late and chronic phases the situation is reversed and interferon-gamma production by T-H1 and T-H0 cells predominates over IL-4 production by T-H2 and T-H0 cells. Understanding of the relationship between the observed biphasic response and clinical manifestation of Ad is important for the development of therapeutic strategies.