Antigen-pulsed dendritic cells expressing macrophage-derived chemokine elicit Th2 responses and promote specific humoral immunity.
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.
Kikuchi
T
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Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
Crystal
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RG
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000918:Antibody Specificity; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000008:administration & dosage; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007114:Immunization; D007116:Immunization, Passive; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014161:Transduction, Genetic
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D019742:Chemokines, CC