Antigen‐Specific Increases in the Number of Splenocytes Expressing MHC Class II Molecules Following Restimulation with Antigen in Various Physical Forms

Bergström-Mollaoglu, M; Lövgren, Karin; Åkerblom, Lennart; Fossum, Caroline; Morein, Brør

doi:10.1111/j.1365-3083.1992.tb03225.x

Cited by 27 publications

(8 citation statements)

References 23 publications

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1997

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The immune responses to immunostimulating complexes (iscoms) containing recombinant Epstein-Barr virus (EBV) gp340 envelope protein was evaluated in BALB/c (H-2 d ) and CBA (H-2 k ) mice. Gp340-iscoms were used either with a low content of Quillaja triterpenoid adjuvant (L-iscoms) or supplemented with additional Quillaja adjuvant in the form of iscomatrix (S-iscoms). Class and subclass distribution of antigp340 antibodies, EBV-neutralizing antibodies, antigen-specific T cell proliferation and cytokine production were determined and these results compared to those obtained by immunization with non-adjuvated gp340. The H-2 d and H-2 k mice were characterized as low or high responders in respect to the level of specific antigp340 antibodies, secretion of IgG2a isotype, antigen-specific lymphoproliferative capacity, interferon-g (IFN-g) and interleukin-10 (IL-10) production in the basic immunizations with gp340. While presentation of the antigen in iscom formulations with low levels of Quillaja triterpenoids induces a moderate enhancement of the immune responses in the low responder H-2 d mice, supplementation with high levels of iscomatrix immunomodulator was required to enhance the immune responses in the high responder H-2 k mice. In both mouse strains subcutaneous immunization with S-iscoms resulted in a significant increase of IgG1-and IgG2a-specific antibodies, as well as in strong antigen-specific proliferative response confirmed by the simultaneous cytokine production. The enhanced antigen-specific secretion of IL-2 and IFN-g together with the abrogation of IL-10 and the absence of IL-4 indicates that the responses were driven towards a Th1-type rather than Th2-type immune response. The S-iscom formulations minimized the differences in immune responses between the two mouse strains, but the capacity of immune sera to neutralize EBV transformation in vitro remained completely strain-dependent. These data indicate that immune responses generated by iscoms can be manipulated by altering the triterpenoid composition of the iscoms and that the levels of triterpenoids can determine whether or not a Th1-type response is made.

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Section: Discussionmentioning

confidence: 99%

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

et al. 1997

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“…Mice injected intraperitoneally with influenza-ISCOMs had a significantly greater proportion of Ia-positive peritoneal cells than mice injected with influenza antigen or Iscom Matrix [71]. Bergström-Mollaoglu et al [72] showed that the frequency of cells expressing MHC class II molecules increased after antigen stimulation in vitro of spleen cells primed by influenza-ISCOMs or HIV gp160-ISCOMs. The increase was antigen dose-specific and at least partly dependent on interferon-␥ (IFN-␥).…”

Section: Uptake and Presentation Of Iscomsmentioning

confidence: 99%

ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

158

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“…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.…”

Section: Discussionmentioning

confidence: 84%

“…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]. Some of these data indicate that macrophages have a relevant role in the enhanced immune response to iscom-borne Ag [18,19].…”

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

Villacrés-Eriksson

1995

Clinical and Experimental Immunology

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SUMMARYInfluenza virus envelope proteins incorporated into immunostimulating complexes (iscoms) are taken up and processed by various kinds of antigen-presenting cells (APC), encompassing peritoneal cells (PEC), unfractionated splenocytes, splenic dendritic cells (DC) or B cells. The iscom-pulsed naive APC stimulated primed T cells to proliferate and produce cytokine in vitro. In contrast, only DC and B cells pulsed with the same antigen (Ag) in the micelle form functioned as accessory cells stimulating the primed T cells to proliferate and produce cytokine. In general, iscoms were better inducers of cell proliferation than micelles, Iscoms stimulated more secretion of IL-2 and interferon-gamma (IFN-7) than the micelles, but both antigenic forms stimulated secretion of IL-4. DC and B cells pulsed with iscoms stimulated most efficiently the secretion of IL-2 and IFN-7, DC were superior to the other APC in stimulating primed T cells to secrete IFN-7. On the other hand, micelles stimulated more efficiently than iscoms splenic T cells from micelleprimed as well as iscom-primed mice to secrete IL-10, These data indicate that influenza virus envelope proteins incorporated in iscoms stimulate a broad T cell response, possibly emphasizing a Thl type of response. The same Ag in a micelle form induce a more prominent Th2 type of T cell response. The results indicate that the administration of an Ag in an adjuvant formulation can superimpose a different cytokine profile on the immune response than that induced by the protein Ag alone.

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Antigen‐Specific Increases in the Number of Splenocytes Expressing MHC Class II Molecules Following Restimulation with Antigen in Various Physical Forms

Cited by 27 publications

References 23 publications

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

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

ISCOMs: an adjuvant with multiple functions

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

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