Epidermal cells enhance interleukin 4 and immunoglobulin E production after stimulation with protein allergen.

Exposure to certain allergens via epithelial tissues is the primary route for the induction of immunoglobulin E-dependent allergies of the immediate type associated with atopic diseases. In order to address the question whether and how epithelial cells might contribute to the induction or increase of TH2-dependent IgE production, we performed co-culture experiments of syngeneic epidermal cells and cells from the associated lymphoid tissue or spleen (responder cells) of BALB/c mice primed with ovalbumin in vivo. In the presence of ovalbumin in vitro, immunoglobulin E but not immunoglobulin G2a production was significantly enhanced by the addition of epidermal cells, and separation of epidermal cells from responder cells by a membrane that prevented cellular contacts or addition of antibodies against intercellular adhesion molecule-1 reduced the enhancement of immunoglobulin E production induced by epidermal cells. Depletion of major histocompatibility complex class II+ antigen presenting Langerhans cells from the epidermal cells prior to co-culture also reduced the enhancement of immunoglobulin E production induced by epidermal cells. The enhanced immunoglobulin E production was dependent on the induction of TH2 cell-derived interleukin-4 detected in co-cultures because it was completely inhibited after addition of anti-interleukin-4 antibodies that also lead to increased immunoglobulin G2a production. Whereas interleukin-4 was not produced by epidermal cells, interleukin-10 seemed to be one important mediator contributed by epidermal cells. Interleukin-10 skewed the response toward a TH2-mediated IgE response because antibodies against interleukin-10 inhibited interleukin-4 and immunoglobulin E production, whereas they enhanced interferon-gamma and immunoglobulin G2a production.

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