Abstract
Influenza 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-gamma) 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-gamma. DC were superior to the other APC in stimulating primed T cells to secrete IFN-gamma. On the other hand, micelles stimulated more efficiently than iscoms splenic T cells from micelle-primed 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 Th1 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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- Afonso L. C., Scharton T. M., Vieira L. Q., Wysocka M., Trinchieri G., Scott P. The adjuvant effect of interleukin-12 in a vaccine against Leishmania major. Science. 1994 Jan 14;263(5144):235–237. doi: 10.1126/science.7904381. [DOI] [PubMed] [Google Scholar]
- Ben-Ahmeida E. T., Potter C. W., Gregoriadis G., Adithan C., Jennings R. IgG subclass response and protection against challenge following immunisation of mice with various influenza A vaccines. J Med Microbiol. 1994 Apr;40(4):261–269. doi: 10.1099/00222615-40-4-261. [DOI] [PubMed] [Google Scholar]
- Bergström-Mollaoglu M., Lövgren K., Akerblom L., Fossum C., Morein B. Antigen-specific increases in the number of splenocytes expressing MHC class II molecules following restimulation with antigen in various physical forms. Scand J Immunol. 1992 Oct;36(4):565–574. doi: 10.1111/j.1365-3083.1992.tb03225.x. [DOI] [PubMed] [Google Scholar]
- Clerici M., Shearer G. M. A TH1-->TH2 switch is a critical step in the etiology of HIV infection. Immunol Today. 1993 Mar;14(3):107–111. doi: 10.1016/0167-5699(93)90208-3. [DOI] [PubMed] [Google Scholar]
- Crowley M., Inaba K., Witmer-Pack M., Steinman R. M. The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. Cell Immunol. 1989 Jan;118(1):108–125. doi: 10.1016/0008-8749(89)90361-4. [DOI] [PubMed] [Google Scholar]
- Ellis J., Chain B. M., Davies D. H., Ibrahim M. A., Katz D. R., Kaye P. M., Lightstone E. Antigen presentation by dendritic cells provides optimal stimulation for the production of interleukin (IL) 2, IL 4 and interferon-gamma by allogeneic T cells. Eur J Immunol. 1991 Nov;21(11):2803–2809. doi: 10.1002/eji.1830211123. [DOI] [PubMed] [Google Scholar]
- Fossum C., Bergström M., Lövgren K., Watson D. L., Morein B. Effect of iscoms and their adjuvant moiety (matrix) on the initial proliferation and IL-2 responses: comparison of spleen cells from mice inoculated with iscoms and/or matrix. Cell Immunol. 1990 Sep;129(2):414–425. doi: 10.1016/0008-8749(90)90217-f. [DOI] [PubMed] [Google Scholar]
- Gimmi C. D., Freeman G. J., Gribben J. G., Sugita K., Freedman A. S., Morimoto C., Nadler L. M. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6575–6579. doi: 10.1073/pnas.88.15.6575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heeg K., Kuon W., Wagner H. Vaccination of class I major histocompatibility complex (MHC)-restricted murine CD8+ cytotoxic T lymphocytes towards soluble antigens: immunostimulating-ovalbumin complexes enter the class I MHC-restricted antigen pathway and allow sensitization against the immunodominant peptide. Eur J Immunol. 1991 Jun;21(6):1523–1527. doi: 10.1002/eji.1830210628. [DOI] [PubMed] [Google Scholar]
- Heinzel F. P., Sadick M. D., Mutha S. S., Locksley R. M. Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7011–7015. doi: 10.1073/pnas.88.16.7011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones P. D., Tha Hla R., Morein B., Lovgren K., Ada G. L. Cellular immune responses in the murine lung to local immunization with influenza A virus glycoproteins in micelles and immunostimulatory complexes (iscoms). Scand J Immunol. 1988 Jun;27(6):645–652. doi: 10.1111/j.1365-3083.1988.tb02397.x. [DOI] [PubMed] [Google Scholar]
- Kanagawa O., Vaupel B. A., Gayama S., Koehler G., Kopf M. Resistance of mice deficient in IL-4 to retrovirus-induced immunodeficiency syndrome (MAIDS) Science. 1993 Oct 8;262(5131):240–242. doi: 10.1126/science.8211142. [DOI] [PubMed] [Google Scholar]
- Kurt-Jones E. A., Beller D. I., Mizel S. B., Unanue E. R. Identification of a membrane-associated interleukin 1 in macrophages. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1204–1208. doi: 10.1073/pnas.82.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
- Levine T. P., Chain B. M. Endocytosis by antigen presenting cells: dendritic cells are as endocytically active as other antigen presenting cells. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8342–8346. doi: 10.1073/pnas.89.17.8342. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linsley P. S., Clark E. A., Ledbetter J. A. T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5031–5035. doi: 10.1073/pnas.87.13.5031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lövgren K., Morein B. The requirement of lipids for the formation of immunostimulating complexes (iscoms). Biotechnol Appl Biochem. 1988 Apr;10(2):161–172. [PubMed] [Google Scholar]
- Macatonia S. E., Taylor P. M., Knight S. C., Askonas B. A. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. doi: 10.1084/jem.169.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morein B., Simons K. Subunit vaccines against enveloped viruses: virosomes, micelles and other protein complexes. Vaccine. 1985 Jun;3(2):83–93. doi: 10.1016/0264-410x(85)90055-6. [DOI] [PubMed] [Google Scholar]
- Morein B., Sundquist B., Höglund S., Dalsgaard K., Osterhaus A. Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses. 1984 Mar 29-Apr 4Nature. 308(5958):457–460. doi: 10.1038/308457a0. [DOI] [PubMed] [Google Scholar]
- Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
- Mowat A. M., Donachie A. M., Reid G., Jarrett O. Immune-stimulating complexes containing Quil A and protein antigen prime class I MHC-restricted T lymphocytes in vivo and are immunogenic by the oral route. Immunology. 1991 Mar;72(3):317–322. [PMC free article] [PubMed] [Google Scholar]
- Nair S., Babu J. S., Dunham R. G., Kanda P., Burke R. L., Rouse B. T. Induction of primary, antiviral cytotoxic, and proliferative responses with antigens administered via dendritic cells. J Virol. 1993 Jul;67(7):4062–4069. doi: 10.1128/jvi.67.7.4062-4069.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
- Romagnani S., Maggi E., Del Prete G. An alternative view of the Th1/Th2 switch hypothesis in HIV infection. AIDS Res Hum Retroviruses. 1994 May;10(5):iii–ix. doi: 10.1089/aid.1994.10.iii. [DOI] [PubMed] [Google Scholar]
- Sypek J. P., Chung C. L., Mayor S. E., Subramanyam J. M., Goldman S. J., Sieburth D. S., Wolf S. F., Schaub R. G. Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response. J Exp Med. 1993 Jun 1;177(6):1797–1802. doi: 10.1084/jem.177.6.1797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi H., Takeshita T., Morein B., Putney S., Germain R. N., Berzofsky J. A. Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. Nature. 1990 Apr 26;344(6269):873–875. doi: 10.1038/344873a0. [DOI] [PubMed] [Google Scholar]
- Trinchieri G. Interleukin-12 and its role in the generation of TH1 cells. Immunol Today. 1993 Jul;14(7):335–338. doi: 10.1016/0167-5699(93)90230-I. [DOI] [PubMed] [Google Scholar]
- Trudel M., Nadon F., Séguin C., Brault S., Lusignan Y., Lemieux S. Initiation of cytotoxic T-cell response and protection of Balb/c mice by vaccination with an experimental ISCOMs respiratory syncytial virus subunit vaccine. Vaccine. 1992;10(2):107–112. doi: 10.1016/0264-410x(92)90026-g. [DOI] [PubMed] [Google Scholar]
- Valensi J. P., Carlson J. R., Van Nest G. A. Systemic cytokine profiles in BALB/c mice immunized with trivalent influenza vaccine containing MF59 oil emulsion and other advanced adjuvants. J Immunol. 1994 Nov 1;153(9):4029–4039. [PubMed] [Google Scholar]
- Villacres-Eriksson M., Bergström-Mollaoglu M., Kåberg H., Lövgren K., Morein B. The induction of cell-associated and secreted IL-1 by iscoms, matrix or micelles in murine splenic cells. Clin Exp Immunol. 1993 Jul;93(1):120–125. doi: 10.1111/j.1365-2249.1993.tb06507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Villacres-Eriksson M., Bergström-Mollaoglu M., Kåberg H., Morein B. Involvement of interleukin-2 and interferon-gamma in the immune response induced by influenza virus iscoms. Scand J Immunol. 1992 Sep;36(3):421–426. doi: 10.1111/j.1365-3083.1992.tb02956.x. [DOI] [PubMed] [Google Scholar]
- Watson D. L., Watson N. A., Fossum C., Lövgren K., Morein B. Interactions between immune-stimulating complexes (ISCOMs) and peritoneal mononuclear leucocytes. Microbiol Immunol. 1992;36(2):199–203. doi: 10.1111/j.1348-0421.1992.tb01657.x. [DOI] [PubMed] [Google Scholar]
- Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
- van Binnendijk R. S., van Baalen C. A., Poelen M. C., de Vries P., Boes J., Cerundolo V., Osterhaus A. D., UytdeHaag F. G. Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition. J Exp Med. 1992 Jul 1;176(1):119–128. doi: 10.1084/jem.176.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]