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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
Published September 15, 2001
Citation Information: J Clin Invest. 2001;108(6):917-927. https://doi.org/10.1172/JCI11564.
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Article

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

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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

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Figure 8

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Immunization with AdMDC/DCs induces protective immunity specific to the ...
Immunization with AdMDC/DCs induces protective immunity specific to the pathogen used for pulsing DCs. (a) P. aeruginosa challenge. C57BL/6 mice were immunized with AdMDC-modified DCs pulsed with heat-killed P. aeruginosa or E. coli (25922 strain). After 3 weeks, immunized animals were infected intratracheally with 2 × 105 CFU P. aeruginosa PAO1 enmeshed in agar beads. (b) E. coli challenge. Immunization of mice was identical to that in a, but 108 CFU E. coli (25922 strain) were used for the intratracheal infection. For both parts, controls included mice without any immunization. Survival was recorded as the percentage of surviving animals (n = 10 mice per group).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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