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.