The induction of cell-associated and secreted IL-1 by iscoms, matrix or micelles in murine splenic cells

Abstract

SUMMARYThe kinetics ofthe expression of membrane-associated IL-1 (mIL-1) and soluble IL-1 (sIL-1) was studied in in vitro stimulated spleen cells from non-primed mice or from mice primed with influenza virus antigens incorporated in the immuno-stimulating complexes (iscoms) or as micelles. Matrix, which is the carrier structure for the antigens in the iscom, was used as a non-antigen stimulus. The IL-1 produced was assayed in an I L-l-dependent cell line and the specificity was demonstrated in a blocking experiment with antiserum to IL-la. Soluble IL-la was also quantified in ELISA. Iscoms and matrix induced production of mIL-1 and sIL-l in cultures from non-treated mice as well as from mice primed 4 days before with iscoms or micelles. Micelles were a less strong stimulus and did not induce production of sIL-1. Micelles induced production of mIL-1 in cultures from non-primed mice or from mice which were recently immunized with micelles. No mIL-l expression was induced by micelles if the spleen cells originated from mice immunized shortly before with iscoms. Depletion experiments demonstrated that sIL-1 was produced by adherent cells upon stimulation with iscoms or matrix. However, factor(s) from the non-adherent cells seem to be necessary for optimal secretion ofslL-1.

Antigen presentation by naive macrophages, dendritic cells and B cells to primed T lymphocytes and their cytokine production following exposure to immunostimulating complexes

“…A higher degree of Ag internalization observed for iscoms compared with micelles [17] is probably a major factor in evoking this enhanced recall response. Another contributing factor is the capacity of iscoms to increase MHC class II expression and enhance the production of IL-1 [18][19][20]. A third enhancing factor is the secretion of the cytokines measured in this study which was Ag-specific since they were only detected following restimulation with the relevant influenza virus Ag.…”

“…Increased expression of MHC class II molecules, considered to be a requirement for efficient Ag presentation, has been observed in primary stimulation of peritoneal cells and also in primed splenocytes upon restimulation with iscoms, both in vivo and in vitro [19,20]. Some of these data indicate that macrophages have a relevant role in the enhanced immune response to iscom-borne Ag [18,19]. We and others have previously demonstrated that immunization with influenza virus iscoms induces the development of T cells secreting IL-2 and IFN-7 [21][22][23].…”

“…Iscoms as well as its matrix, i.e. the iscom structure devoid of protein, stimulate the secretion of IL-1 by murine splenocytes and peritoneal cells [18]. Increased expression of MHC class II molecules, considered to be a requirement for efficient Ag presentation, has been observed in primary stimulation of peritoneal cells and also in primed splenocytes upon restimulation with iscoms, both in vivo and in vitro [19,20].…”

Coadministration of Polyinosinic:Polycytidylic Acid and Immunostimulatory Complexes Modifies Antigen Processing in Dendritic Cell Subsets and Enhances HIV Gag-Specific T Cell Immunity

“…ISCOMs induce production of IL-1β (24, 25), which promotes induction of Th17 CD4 T cells in combination with IL-6 (49), and induction of IL-17+ CD4 T cells has been observed after ISCOM vaccination (50). We did not detect IL-17 production after vaccination with Poly I:C alone, but did detect low and comparable frequencies of IL-17+ CD4 T cells after ISCOM vaccination, with or without Poly I:C in several experiments (Fig.…”

“…ISCOMs can enhance antigen delivery to APCs when antigen is incorporated into the particle but ISCOMs do not function solely as delivery vehicles, since certain fractions of saponin possess intrinsic adjuvant activity (23). ISCOMs have been shown to induce caspase-dependent cleavage of IL-1β and robust serum production of IL-5, IL-6, GM-CSF and IL-12 p40 (24, 25). As a result, ISCOMs prime potent long-lived antibody responses with a balanced CD4 Th1/Th2 T cell response (26), and low-level induction of CTLs.…”