Antigen-pulsed dendritic cells expressing macrophage-derived chemokine elicit Th2 responses and promote specific humoral immunity
Toshiaki Kikuchi, Ronald G. Crystal
Toshiaki Kikuchi, Ronald G. Crystal
View: Text | PDF
Article

Antigen-pulsed dendritic cells expressing macrophage-derived chemokine elicit Th2 responses and promote specific humoral immunity

Abstract

Macrophage-derived chemokine (MDC) is a potent chemoattractant for antigen-specific T lymphocytes. We hypothesized that Adenovirus- (Ad-) transduced dendritic cells (DCs) overexpressing MDC would enhance the T cell–mediated humoral immune response specific for antigens presented by the DC. We challenged two strains of mice with lethal Pseudomonas aeruginosa infection 3 weeks after immunization with AdMDC-modified DCs pulsed with heat-killed P. aeruginosa. MDC-expressing DCs specifically attracted T lymphocytes and preserved typical DC surface phenotypes without growth factors in vitro. Mice immunized with AdMDC/Pseudomonas/DCs developed high levels of serum anti-Pseudomonas Ab’s and were protected from a lethal respiratory challenge with Pseudomonas. The in vivo protective immunity required CD4+ T cells, B cells, and IL-4, but not CD8+ T cells and IL-12. AdMDC/DCs pulsed with Pseudomonas yielded significant but not absolute cross-protection against different strains of P. aeruginosa. Pseudomonas-pulsed AdMDC/DCs protected mice from Pseudomonas but not Escherichia coli and vice versa; this microbe-specific protection correlated with microbe-specific induction of CD4+ T cell proliferation and IL-4 secretion. Based on these observations, AdMDC-modified DCs pulsed with a killed bacteria may be a useful approach to vaccination against infectious disorders.

Authors

Toshiaki Kikuchi, Ronald G. Crystal

×

Figure 9

Options: View larger image (or click on image) Download as PowerPoint
Cross-protective immunity of AdMDC-modified DCs against laboratory or cl...
Cross-protective immunity of AdMDC-modified DCs against laboratory or clinical strains of P. aeruginosa. (a and b) Immunization resulting from AdMDC-modified DCs pulsed with laboratory strains of Pseudomonas. C57BL/6 mice were immunized with AdMDC-modified DCs pulsed with heat-killed P. aeruginosa laboratory strains PAO1, PAO-NP, PAK, or PA103 at 105 DCs per mouse. Three weeks after immunization, mice were challenged intratracheally with 2 × 105 CFU P. aeruginosa laboratory PAO1 strain (a) or clinical PA514 strain (b) enmeshed in agar beads. (c and d) Immunization resulting from AdMDC-modified DCs pulsed with clinical strains of Pseudomonas. C57BL/6 mice were immunized with AdMDC-modified DCs pulsed with heat-killed P. aeruginosa clinical strains PA514, PA515, PA516, or PA517 at 105 DCs per mouse. Three weeks after immunization, mice were challenged intratracheally with 2 × 105 CFU P. aeruginosa laboratory PAO1 strain (d) or clinical PA514 strain (c) enmeshed in agar beads. In all parts, controls included naive mice without any immunization. Survival was recorded as the percentage of surviving animals (n = 10 mice per group).