Dendritic cells genetically modified to express CD40 ligand and pulsed
with antigen can initiate antigen-specific humoral immunity independent of
CD4+ T cells
Toshiaki Kikuchi1, Stefan Worgall1, 2, Ravi Singh3, Malcolm A.S. Moore5
& Ronald G Crystal1, 3, 4
1
Division of Pulmonary and Critical Care Medicine of
the Department of Medicine, Weill Medical College of Cornell University,
New York, New York, USA
2
Department of Pediatrics, Weill Medical College of
Cornell University, New York, New York, USA
3
Belfer Gene Therapy Core Facility, Weill Medical College
of Cornell University, New York, New York,
USA
4
Institute of Genetic Medicine, Weill Medical College
of Cornell University, New York, New York,
USA
5
James Ewing Laboratory of Developmental Hematopoiesis
Memorial Sloan-Kettering Cancer Center, New York, New
York, USA
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.
