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

被引:209
作者
Boscardin, SB
Hafalla, JCR
Masilamani, RF
Kamphorst, AO
Zebroski, HA
Rai, U
Morrot, A
Zavala, F
Steinman, RM
Nussenzweig, RS
Nussenzweig, MC
机构
[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA
[2] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA
[3] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[4] NYU, Sch Med, Dept Med & Mol Parasitol, New York, NY 10016 USA
[5] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
[6] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
关键词
D O I
10.1084/jem.20051639
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:599 / 606
页数:8
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