Activation of dendritic cells and induction of CD4+ T cell differentiation by aluminum-containing adjuvants

Anna Sokolovska, Stanley L. Hem, Harm HogenEsch

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Aluminum-containing adjuvants are widely used in licensed human and veterinary vaccines. However, the mechanism by which these adjuvants enhance the immune response and predominantly stimulate a TH2 humoral immune response is not well understood. In this study, the effects of aluminum hydroxide and aluminum phosphate adjuvants on antigen presentation, expression of costimulatory molecules and cytokines by mouse dendritic cells (DCs) and the ability of DCs to induce T helper cell differentiation were investigated. Dendritic cells pulsed with ovalbumin (OVA) adsorbed to aluminum-containing adjuvants activated antigen-specific T cells more effectively than DCs pulsed with OVA alone. Aluminum hydroxide adjuvant had a significantly stronger effect than aluminum phosphate adjuvant. Both aluminum-containing adjuvants significantly increased the expression of CD86 on DCs but only aluminum hydroxide adjuvant also induced moderate expression of CD80. Aluminum-containing adjuvants stimulated the release of IL-1β and IL-18 from DCs via caspase-1 activation. DCs incubated with LPS and OVA induced TH1 differentiation of naïve CD4+ T cells. In contrast, DCs incubated with aluminum/OVA activated CD4+ T cells to secrete IL-4 and IL-5 as well as IFN-γ. Addition of neutralizing anti-IL-1β antibodies decreased IL-5 production and addition of anti-IL-18 antibodies decreased both IL-4 and IL-5 production. Inhibition of IL-1β and IL-18 secretion by DCs via inhibition of caspase-1 also led to a marked decrease of IL-4 and IL-5 by CD4+ T cells. These results indicate that aluminum-containing adjuvants activate DCs and influence their ability to direct TH1 and TH2 responses through the secretion of IL-1β and IL-18.

Original languageEnglish (US)
Pages (from-to)4575-4585
Number of pages11
JournalVaccine
Volume25
Issue number23
DOIs
StatePublished - Jun 6 2007
Externally publishedYes

Fingerprint

dendritic cells
Aluminum
cell differentiation
Dendritic Cells
adjuvants
aluminum
Cell Differentiation
T-lymphocytes
T-Lymphocytes
interleukin-18
interleukin-5
Interleukin-18
Interleukin-5
ovalbumin
Ovalbumin
interleukin-1
Interleukin-1
Aluminum Hydroxide
aluminum hydroxide
interleukin-4

Keywords

  • Adjuvants
  • Dendritic cells
  • T helper cell differentiation

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Activation of dendritic cells and induction of CD4+ T cell differentiation by aluminum-containing adjuvants. / Sokolovska, Anna; Hem, Stanley L.; HogenEsch, Harm.

In: Vaccine, Vol. 25, No. 23, 06.06.2007, p. 4575-4585.

Research output: Contribution to journalArticle

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