T cell-dependent secretion of IL-1 beta by a dendritic cell line (XS52) derived from murine epidermis.
IL-1 beta 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-1 beta 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-1 beta mRNA. We sought to determine whether XS52 cells secrete IL-1 beta upon Ag-dependent interaction with T cells and, if so, to elucidate the mechanism. Despite constitutive expression of mRNA for both IL-1 beta and the IL-1 beta-converting enzyme (ICE), XS52 cells secreted no detectable IL-1 beta spontaneously. When they were cultured with HDK-1 T cells and KLH, relatively large amounts of IL-1 beta (17.5-kDa form) were detected in the culture supernatant. IL-1 beta was secreted by LPS-stimulated XS52 cells, but not by LPS- or Con A-stimulated HDK-1 cells, suggesting that IL-1 beta is secreted primarily by XS52 cells in the coculture system. Incubation with HDK-1 cells alone or with KLH alone caused no IL-1 beta secretion, indicating the requirement for both T cells and Ag. IL-1 beta secretion was associated with a striking up-regulation of IL-1 beta mRNA and a modest up-regulation of ICE mRNA and enzymatic activity. IL-1 beta secretion was blocked by Ac-YVAD-CHO (a peptide inhibitor of ICE), CTLA4-Ig fusion protein, or anti-Ia mAb. IL-1 beta 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-1 beta upon Ag-dependent interaction with T cells, with both Ia molecules and B7-related molecules playing essential roles.
Kitajima
T
T
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Ariizumi
K
K
Mohamadazadeh
M
M
Edelbaum
D
D
Bergstresser
P R
PR
Takashima
A
A
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism*; D004817:Epidermis / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007375:Interleukin-1