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

Nature Medicine volume 6, pages 1154–1159 (2000)Cite this article

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.

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Figure 1: Activation of dendritic cells by genetic modification with the mouse CD40L cDNA.
Figure 2: Nonspecific B-cell proliferation induced by co-culture of mCD40L-modified DCs and syngeneic B cells.
Figure 3: Ability of AdmCD40L-modified DCs pulsed with P. aeruginosa to directly induce naive B cells to secrete P. aeruginosa-specific antibody in vitro in the absence of CD4+ T cells.
Figure 4: P. aeruginosa-specific antibodies generated in vivo in wild-type mice immunized with AdmCD40L-modified DCs pulsed with Pseudomonas.
Figure 5: P. aeruginosa-specific antibodies generated in CD4−/− C57Bl/6 mice immunized with AdmCD40L-modified DCs pulsed with Pseudomonas.immunized CD4−/− mice, n; immunized wild-type mice, ¤; immunized wild-type mice, non-immunized wild-type mice, ▨.
Figure 6: Mice immunized with AdmCD40L-modified DCs pulsed with P. aeruginosa develop Pseudomonas-specific, CD4+ T cell-independent, B cell-dependent protection against lethal bronchopulmonary infection of P. aeruginosa.

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Acknowledgements

We thank N. Mohamed for help in preparing this manuscript. These studies were supported, in part, by National Institutes of Health grant P01 HL51746-06A1, the Will Rogers Memorial Fund (Los Angeles, California), the Cystic Fibrosis Foundation (Bethesda, Maryland) and GenVec (Gaithersburg, Maryland).

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine of the Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA

    Toshiaki Kikuchi, Stefan Worgall & Ronald G Crystal

  2. Department of Pediatrics, Weill Medical College of Cornell University, New York, New York, USA

    Stefan Worgall

  3. Belfer Gene Therapy Core Facility, Weill Medical College of Cornell University, New York, New York, USA

    Ravi Singh & Ronald G Crystal

  4. Institute of Genetic Medicine, Weill Medical College of Cornell University, New York, New York, USA

    Ronald G Crystal

  5. James Ewing Laboratory of Developmental Hematopoiesis Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Malcolm A.S. Moore

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  1. Toshiaki Kikuchi
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Correspondence to Ronald G Crystal.

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Kikuchi, T., Worgall, S., Singh, R. et al. Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells. Nat Med 6, 1154–1159 (2000). https://doi.org/10.1038/80498

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