The Journal of Experimental Medicine
StemCell Technologies
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Published online 27 February 2006 doi:10.1084/jem.20051639
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 3, 599-606
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ARTICLE

 Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses

Silvia B. Boscardin1, Julius C.R. Hafalla4, Revati F. Masilamani1, Alice O. Kamphorst1, Henry A. Zebroski2, Urvashi Rai4, Alexandre Morrot5, Fidel Zavala5, Ralph M. Steinman2, Ruth S. Nussenzweig4, and Michel C. Nussenzweig1,3

1 Laboratory of Molecular Immunology, 2 Laboratory of Cellular Physiology and Immunology, and 3 Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
4 Department of Medical and Molecular Parasitology, and Department of Pathology, New York University School of Medicine, New York, NY 10016
5 Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205

CORRESPONDENCE M.C. Nussenzweig: nussen{at}rockefeller.edu.

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.

Abbreviations used: CSP, circumsporozoite protein; NP, (4-hydroxy-3-nitrophenyl) acetyl.


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