IL-1 beta is essential for Langerhans cell activation and antigen deliveryto the lymph nodes during contact sensitization: Evidence for a dermal source of IL-1 beta

IL-1 beta (-/-) mice manifest an impaired contact hypersensitivity response to the hapten trinitrochlorobenzene, with the principle defect expressed d uring the sensitization phase of this response. Following application of ha pten to the skin, epidermal Langerhans cells of IL-beta (-/-) mice failed t o demonstrate the classical phenotype of activation. In addition, the deliv ery of epicutaneously applied fluorescein isothiocyanate to draining lymph nodes was decreased in IL-1 beta (-/-) mice. Hapten delivery to draining ly mph nodes could be restored by intradermal injection of recombinant IL-1 be ta. Reconstitution of lethally irradiated IL-1 beta (-/-) mice by transfer of wild-type bone marrow restored hapten-stimulated IL-1 beta mRNA expressi on, demonstrating that IL-1 beta production was dependent on bone marrow-de rived cells. In wild-type skin, IL-1 beta expression was upregulated in a t ime- and dose-dependent fashion following hapten application. Interestingly , prominent IL-1 beta expressing cells were found in the dermis, suggesting that dermal cells may contribute significantly to the contact hypersensiti vity response. (C) 2001 Academic Press.