IL-1β has been reported to play an essential role in the induction of T cell-mediated immune responses in skin, and Langerhans cells are considered to be the primary source of IL-1β in epidermis. We have established recently a long-term dendritic cell line (XS52) from mouse epidermis. This line resembles resident epidermal Langerhans cells in many respects, including the potent capacity to present a protein Ag (KLH) to a CD4+ Th1 clone (HDK-1) and the expression of IL-1β mRNA. We sought to determine whether XS52 cells secrete IL-1β upon Ag-dependent interaction with T cells and, if so, to elucidate the mechanism. Despite constitutive expression of mRNA for both IL- 1β and the IL-1β-converting enzyme (ICE), XS52 cells secreted no detectable IL-1β spontaneously. When they were cultured with HDK-1 T cells and KLH, relatively large amounts of IL-1β (17.5-kDa form) were detected in the culture supernatant. IL-1β was secreted by LPS-stimulated XS52 cells, but not by LPS- or Con A-stimulated HDK-1 cells, suggesting that IL-1β is secreted primarily by XS52 cells in the coculture system. Incubation with HDK-1 cells alone or with KLH alone caused no IL-1β secretion, indicating the requirement for both T cells and Ag, IL-1β secretion was associated with a striking up-regulation of IL-1β mRNA and a modest up-regulation of ICE mRNA and enzymatic activity. IL-1β secretion was blocked by Ac-YVAD-CHO (a peptide inhibitor of ICE), CTLA4-Ig fusion protein, or anti-Ia mAb. IL-1β secretion was triggered in a T cell-independent manner by either CTLA4-Ig or anti-Ia mAb in immobilized forms. Thus, the XS52 dendritic cell line secretes, by an ICE-dependent mechanism, biologically relevant amounts of IL- 1β upon Ag-dependent interaction with T cells, with both Ia molecules and B7-related molecules playing essential roles.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1995|
ASJC Scopus subject areas
- Immunology and Allergy