Dendritic Cell Secretion of IL-15 Is Induced by Recombinant huCD40LT and Augments the Stimulation of Antigen-Specific Cytolytic T Cells

• Published in: Cellular immunology Vol. 193; no. 1; pp. 48 - 58
• Main Authors: Kuniyoshi, Jon S., Kuniyoshi, Catherine J., Lim, Amy M., Wang, Flora Y., Bade, Elizabeth R., Lau, Roy, Thomas, Elaine K., Weber, Jeffrey S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 10.04.1999
• Subjects: antigen presentation; Antigens - immunology; CD40 Ligand; CD40L; Cell Line; dendritic cells; Dendritic Cells - metabolism; HLA-A2 Antigen - immunology; Humans; IL-15; Interferon-gamma - pharmacology; Interleukin-12 - biosynthesis; Interleukin-15 - biosynthesis; Melanoma - immunology; Membrane Glycoproteins - pharmacology; Recombinant Proteins - pharmacology; T-Lymphocytes, Cytotoxic - immunology; tumor antigens; CD40L; IL-15; dendritic cells; antigen presentation; tumor antigens
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1999.1469

Dendritic cells (DC) are professional antigen-presenting cells which stimulate strong proliferative and cytolytic T cell responses. Stimulation of CD40 on dendritic cells by its ligands and anti-CD40 antibodies induces maturation and enhances DC stimulatory ability. In order to understand the mechanism by which ligand:CD40 interactions augment DC function, we assessed the role of T cell stimulatory cytokines IL-12 and IL-15 in the function of DC stimulated with soluble trimeric CD40L, a recombinant fusion protein incorporating three covalently linked extracellular CD40L domains (huCD40LT). Peripheral blood derived DC treated with huCD40LT and/or IFN-γ were used to stimulate T cell responsesin vitroto specific antigens. DC treated with huCD40LT or IFN-γ/huCD40LT stimulated enhanced T cell proliferation to CASTA, a soluble protein fromC. albicans,induced T cells with augmented antigen-specific lysis, and increased the yield of antigen-specific IFN-γ-producing T cells. IL-15 production by DC was enhanced in cultures treated with huCD40LT and correlated with expansion of antigen-specific cytolytic T cells. Addition of a neutralizing anti-IL-15 monoclonal antibody inhibited the expansion of viral and tumor antigen-specific T cells stimulated by IFN-γ and huCD40LT-treated DC. In contrast, this enhanced stimulatory ability of DC did not appear to depend on synthesis of IL-12 since huCD40LT treatment stimulated the generation of antigen-specific cytokine producing and cytolytic T cells without increased IL-12 production. Addition of anti-IL-12 monoclonal antibody did not inhibit expansion of these cells. These data suggest that production of IL-15 but not IL-12 is an important factor in the enhanced immunostimulatory ability of huCD40LT-treated DC.