The Journal of Immunology, Vol 155, Issue 8 3794-3800, Copyright © 1995 by American Association of Immunologists

ARTICLES

T cell-dependent secretion of IL-1 beta by a dendritic cell line (XS52) derived from murine epidermis

T Kitajima, K Ariizumi, M Mohamadazadeh, D Edelbaum, PR Bergstresser and A Takashima
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.

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.

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