Advertisement

Determining Adjuvant Activity on T-Cell Function In Vivo: Th Cells

  • Thomas Lindenstrøm
  • Peter Andersen
  • Else Marie Agger
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 626)

Abstract

Adjuvants constitute a critical component in vaccine development in terms of both stimulating and directing immune responses of a suitable profile to promote protection against a diverse range of disease targets. In the past, the field of adjuvant research was mainly dominated by empirical testing and serendipity. However, there is a strong need to develop new generations of adjuvants based on rational design, as well as a requirement to characterise and comprehend their mechanism(s) of action. Adjuvant development can be characterised as an iterative process where potential candidates are repeatedly tested in vitro and in vivo for immunogenicity and optimised in terms of formulation and delivery. Novel lead candidates of adjuvants with a suitable immunological profile relative to specific disease targets are subsequently selected and evaluated in efficacy studies. A central aspect in such a development and selection process is to determine the adjuvant activity on T-cell function in vivo. Expanding our knowledge on these mechanisms will improve our chance of developing new successful vaccines designed to target specific diseases.

Key words

Adjuvants T-cell polarisation antigen recall cytokine profile T-cell frequency T-cell proliferation multifunctional T cells 

Notes

Acknowledgments

Linda Christensen and Maria Nørtoft Sørensen are acknowledged for their excellent technical assistance. We are indebted to all colleagues, present and former, at the Department of Infectious Disease Immunology for input to the described protocols.

References

  1. 1.
    Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M., Hoffmann, J. A. (1996) The dorsoventral regulatory gene cassette spatzle/toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973–983.PubMedCrossRefGoogle Scholar
  2. 2.
    Medzhitov, R., PrestonHurlburt, P., Janeway, C. A. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394–397.PubMedCrossRefGoogle Scholar
  3. 3.
    Hargreaves, D. C., Medzhitov, R. (2005) Innate sensors of microbial infection. J Clin Immunol 25, 503–510.PubMedCrossRefGoogle Scholar
  4. 4.
    Garcon, N., Chomez, P., Van Mechelen, M. (2007) GlaxoSmithKline Adjuvant systems in vaccines: concepts, achievements and perspectives. Expert Rev Vaccines 6, 723–739.PubMedCrossRefGoogle Scholar
  5. 5.
    Mosca, F., Tritto, E., Muzzi, A., Monaci, E., Bagnoli, F., Iavarone, C., et al. (2008) Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA 105, 10501–10506.PubMedCrossRefGoogle Scholar
  6. 6.
    Seubert, A., Monaci, E., Pizza, M., O’Hagan, D. T., Wack, A. (2008) The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol 180, 5402–5412.PubMedGoogle Scholar
  7. 7.
    Schellack, C., Prinz, K., Egyed, A., Fritz, J. H., Wittmann, B., Ginzler, M., et al. (2006) IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses. Vaccine 24, 5461–5472.PubMedCrossRefGoogle Scholar
  8. 8.
    Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., et al. (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9, 847–856.PubMedCrossRefGoogle Scholar
  9. 9.
    Korsholm, K. S., Agger, E. M., Foged, C., Christensen, D., Dietrich, J., Andersen, C. S., et al. (2007) The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes. Immunology 121, 216–226.PubMedCrossRefGoogle Scholar
  10. 10.
    Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., Coffman, R. L. (1986) Two types of murine helper T cell clone. 1. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136, 2348–2357.PubMedGoogle Scholar
  11. 11.
    Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., et al. (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6, 1123–1132.PubMedCrossRefGoogle Scholar
  12. 12.
    Lyons, A. B., Parish, C. R. (1994) Determination of lymphocyte division by flow-cytometry. J Immunol Methods 171, 131–137.PubMedCrossRefGoogle Scholar
  13. 13.
    Seder, R. A., Darrah, P. A., Roederer, M. (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8, 247–258.PubMedCrossRefGoogle Scholar
  14. 14.
    Gauduin, M. C., Kaur, A., Ahmad, S., Yilma, T., Lifson, J. D., Johnson, R. P. (2004) Optimization of intracellular cytokine staining for the quantitation of antigen-specific CD4+ T cell responses in rhesus macaques. J Immunol Methods 288, 61–79.PubMedCrossRefGoogle Scholar
  15. 15.
    Horton, H., Thomas, E. P., Stucky, J. A., Frank, I., Moodie, Z., Huang, Y. D., et al. (2007) Optimization and validation of an 8-color intracellular cytokine staining (ICS) assay to quantify antigen-specific T cells induced by vaccination. J Immunol Methods 323, 39–54.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Thomas Lindenstrøm
    • 1
  • Peter Andersen
    • 1
  • Else Marie Agger
    • 1
  1. 1.Adjuvant Research, Department of Infectious Disease ImmunologyStatens Serum InstitutCopenhagenDenmark

Personalised recommendations