Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells

Toshiaki Kikuchi, Stefan Worgall, Ravi Singh, Malcolm A.S. Moore, Ronald Crystal

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

We have investigated whether dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can trigger B cells to produce antigen-specific antibodies without CD4+ T-cell help. Dendritic cells modified with a recombinant adenovirus vector to express CD40 ligand and pulsed with heat-killed Pseudomonas induced naive B cells to produce antibodies against Pseudomonas in the absence of CD4+ T cells in vitro, initiated Pseudomonas-specific humoral immune responses in vivo in wild-type and CD4(-/-) mice, and protected immunized wild-type and CD4(-/-), but not B-cell(-/-) mice, from lethal intrapulmonary challenge with Pseudomonas. Thus, genetic modification of dendritic cells with CD40 ligand enables them to present a complex mixture of microbial antigens and establish CD4+ T cell-independent, B cell-mediated protective immunity against a specific microbe.

Original languageEnglish
Pages (from-to)1154-1159
Number of pages6
JournalNature Medicine
Volume6
Issue number10
DOIs
Publication statusPublished - 2 Nov 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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