6533b7d9fe1ef96bd126c3bb

RESEARCH PRODUCT

Signals involved in the early TH1/TH2 polarization of an immune response depending on the type of antigen.

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Abstract Background: The early production of distinct cytokines by epidermal cells (ECs) in response to antigen exposure may govern the development of T H1 -like immune responses, such as contact sensitivity, or T H2 -like immune responses, such as IgE-dependent allergies of the immediate type, depending on the type of antigen. Objective: The aim of this study was to compare the signals induced by protein allergens with those induced by haptens in ECs and subsequently in local draining lymph node cells (LNCs) or splenocytes. Methods: BALB/c mice were primed in vivo with the protein allergens ovalbumin or birch pollen or the haptens 2,4-dinitrofluorobenzene or trinitrochlorbenzene, respectively, and cytokine and immunoglobulin secretions of responding splenocytes were measured by ELISA after in vitro coculture with ECs. Induction of cytokine mRNA expression in ECs and LNC s was analyzed by reverse transcriptase-PCR. Results: In the presence of protein allergens, ECs enhance the induction of a T H2 immune response (IL-4 and IgE production of splenocytes), whereas a T H1 immune response (IFN-γ and IgG 2a production) was only induced in the context of haptens. Heat inactivation of ovalbumin did not diminish the development of a T H2 immune response. One direct effect of antigen on ECs was the earlier expression of IL-10 mRNA after stimulation with protein allergens (30 minutes) than with haptens (2 hours) in vitro. By using an in vivo approach, sensitization of the skin with trinitrochlorbenzene, but not with ovalbumin, resulted in an early induction of IL-1β, IL-12p40, and IFN-γ mRNA in LNCs, whereas IL-18 was induced by both. Conclusion: These data indicate that the type of antigen strongly influences the type of immune response by eliciting distinct signals already in the epithelium. (J Allergy Clin Immunol 1999;103:298-306.)