Involvement of Interleukin‐2 and Interferon‐Gamma in the Immune Response Induced by Influenza Virus Iscoms

Abstract

Splenocytes from mice primed with influenza virus envelope proteins incorporated in iscoms, as micelles or as infectious virus, were restimulated in vitro with the same antigen. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were assayed in the supernatants of such cultures. Influenza virus iscoms induced IL-2 and IFN-gamma responses in restimulation experiments that were antigen specific and significantly higher than those induced by micelles or infectious virus. Serum samples collected at the end of the experiments were analysed for the antibody response and profile. The antibody titres induced by iscoms were of a similar order of magnitude as those induced by infectious virus, and were about 18 times higher than the titres induced by micelles. In mice immunized with iscoms or infectious virus the most abundant antibodies were of the IgG1 and IgG2a isotype, and the IgE response was low. We conclude that immunization with iscoms stimulates the Th1-like subtype of murine T lymphocytes.

Influence of Quillaja saponaria Triterpenoid Content on the Immunomodulatory Capacity of Epstein–Barr Virus Iscoms

“…There was simultaneous production of IL-2 and IFN-g in spleen cultures of both mouse strains. Although the ability of iscoms and other adjuvants to induce a cytokine response has not been fully clarified [26,34], previous reports have documented that many iscom formulations stimulate the secretion of IL-2 and IFN-g in vivo [35,36] and in vitro [37], and that during immunization, saponin increases the expression of class II molecules on antigen-presenting cells [38]. In addition, it is known that immunization with proteins incorporated into iscom formulations which promote protein translocation into the cytosol succeeds in generating CD8 + CTL in vivo [39,40].…”

ISCOMs: an adjuvant with multiple functions

“…One important question is which cell populations contribute to the production of cytokines after immunization with ISCOMs. Experiments with spleen cells from mice immunized with OVA-ISCOMs or influenza-ISCOMs have shown that depletion of CD4 ϩ T cells before antigen stimulation in vitro abrogates several antigen-specific cellular activities, including proliferation and secretion of IL-2, IL-10, and IFN-␥ [87][88][89]. Likewise, depletion of CD4 ϩ T cells after antigen stimulation of spleen cells primed with PSA-2-ISCOMs removed all IL-4-secreting and 90% of the IFN-␥-secreting cells as determined by ELISPOT [28].…”

“…Production of IL-2 was first observed in a study by Fossum et al [86] and has been demonstrated after immunization with several antigens in ISCOMs, including influenza antigen [77,80,82,86,87], OVA [88,89], HSV type 1 glycoproteins [90], and EBV gp340 [91]. Immunization with ISCOMs containing these antigens [77,80,82,[87][88][89][90][91], or antigens from the parasites L. major [28,92,93] [76].…”

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

“…Also, increased numbers of cells bearing MHC class II molecules were observed after treatment with iscoms [18,19]. In mice immunized with iscoms, memory T cells are recruited in an antigenspecific manner, producing IL-2 and interferon-gamma (IFN-y) upon restimulation [20,21]. These effects and the transient high spontaneous proliferation of murine splenocytes cultured with matrix or iscom [20] may be partly due to induction of IL-I; these results led us to address the question ofthe effect of iscoms or matrix on APC and their secretion of monokines.…”