IL-1 alpha, but not IL-1 beta, is required for contact-allergen-specific Tcell activation during the sensitization phase in contact hypersensitivity

Contact hypersensitivity (CHS) is a T cell-mediated cellular immune respons e caused by epicutaneous exposure to contact allergens. In this reaction, a fter the first epicutaneous allergen sensitization, Langerhans cells (LC) c atch allergens and migrate from the skin to draining lymph nodes (LN) and a ctivate naive T cells. Although IL-1 is suggested to be involved in these p rocesses, the mechanisms have not been elucidated completely. In this repor t, to elucidate roles of IL-1 alpha and IL-1 beta in CHS, we analyzed ear s welling in 2,4,6-trinitrochlorobenzene (TNCB)-induced CHS using gene-target ed mice. We found that ear swelling was suppressed in IL-1 alpha -deficient (IL-1 alpha (-/-)) mice but not in IL-1 beta (-/-) mice. LC migration from the skin into LN was delayed in both IL-1 alpha (-/-) and IL-1 beta (-/-) mice, suggesting that this defect was not the direct cause for the reduced CHS in these mice. However, we found that the proliferative response of tri nitrophenyl (TNP)-specific T cells after sensitization with TNCB was specif ically reduced in IL-1 alpha (-/-) mice. Furthermore, adoptive transfer of TNP-conjugated IL-1-deficient epidermal cells (EC) into wild-type mice indi cated that only IL-1 alpha, but not IL-1 beta, produced by antigen-presenti ng cells in EC could prime allergen-specific T cells. These observations in dicate that IL-1 alpha, but not IL-1 beta, plays a crucial role in TNCB-ind uced CHS by sensitizing TNP-specific T cells.