Anatomical Origin of Dendritic Cells Determines Their Life Span in Peripheral Lymph Nodes

Ruedl, Christiane; Koebel, Pascale; Bachmann, Martin F.; Hess, Michael W.; Karjalainen, Klaus

doi:10.4049/jimmunol.165.9.4910

Cited by 191 publications

(179 citation statements)

References 42 publications

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“…Considering steady-state and immunization-induced DC turnover [21][22][23] in LN, this persistence of vaccine-bearing DC in LN is consistent with continuous replenishment from the site of immunization. Indeed, a single wave of DC migration would result in decreased number of vaccine-labeled cells in the LN over time.…”

Section: Discussionmentioning

confidence: 59%

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

et al. 2008

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Vaccine efficacy largely depends upon DC targeting and activation. The most potent TLR soluble ligands induce diffuse DC activation, which may be associated with marked pro‐inflammatory responses and possibly adverse effects. This raises the concern that effective vaccine adjuvants may similarly rely on widespread DC activation. Using a promising candidate vaccine against tuberculosis (fusion protein of Ag85B and 6‐kDa early secretory antigenic target (ESAT‐6)) formulated in the potent IC31® adjuvant, DC targeting and activation was studied in vivo, following the fate of antigen and adjuvant in the draining lymph nodes, to define the magnitude of DC targeting/activation required in vivo to induce protective vaccine responses. Unexpectedly, protective IFN‐γ‐mediated Ag85B‐ESAT‐6/IC31® responses were associated to the activation of a minute population (less than 0.3%) of CD11c+ lymph node DC, without detectable systemic pro‐inflammatory responses. This activated peripheral tissue‐derived DC population, characterized by enhanced CD80, CD86, CD40 and IL‐12p40 expression, was only identified when focusing on adjuvant‐ or antigen‐labeled CD11c+ DC, which were found to support T cell proliferation. Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen‐associated DC but without detectable enhancement of CD80, CD86, CD40 or IL‐12p40 expression. Thus, potent protective IFN‐γ‐producing responses may be elicited by the exquisite activation of a minute number of in vivo targeted DC.

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Section: Discussionmentioning

confidence: 59%

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

et al. 2008

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“…4 and 5). This difference may be due to the high frequencies of Langerhans cells present in the epidermis in particular, because this lineage of DC is very efficient in taking up skin-derived Ags for T cell stimulation (47). However, although for these reasons intradermal vaccinations may be considered attractive for vaccination, this technique may not represent a preferred immunization route because of the technical difficulties involved in its use in humans.…”

Section: Discussionmentioning

confidence: 99%

Critical Role for Activation of Antigen-Presenting Cells in Priming of Cytotoxic T Cell Responses After Vaccination with Virus-Like Particles

Storni¹,

Lechner²,

Erdmann³

et al. 2002

The Journal of Immunology

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113

111

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Virus-like particles (VLPs) are known to induce strong Ab responses in the absence of adjuvants. In addition, VLPs are able to prime CTL responses in vivo. To study the efficiency of this latter process, we fused peptide p33 derived from lymphocytic choriomeningitis virus to the hepatitis B core Ag, which spontaneously assembles into VLPs (p33-VLPs). These p33-VLPs were efficiently processed in vitro and in vivo for MHC class I presentation. Nevertheless, p33-VLPs induced weak CTL responses that failed to mediate effective protection from viral challenge. However, if APCs were activated concomitantly in vivo using either anti-CD40 Abs or CpG oligonucleotides, the CTL responses induced were fully protective against infection with lymphocytic choriomeningitis virus or recombinant vaccinia virus. Moreover, these CTL responses were comparable to responses generally induced by live vaccines, because they could be measured in primary ex vivo 51Cr release assays. Thus, while VLPs alone are inefficient at inducing CTL responses, they become very powerful vaccines if applied together with substances that activate APCs.

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“…For many years the macrophage has been regarded as the main accessory cell for the immune response. Later it has became evident that dendritic cells (DCs) can also act as a very potent APC [3,4]. They express large amounts of surface class II HLA antigens [5] particularly HLA-DR and lack macrophage differentiation antigens like CD14 or CD68 [6,7].…”

Section: Introductionmentioning

confidence: 99%

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Bălănescu

Radu

Nat

et al. 2002

J Cellular Molecular Medi

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Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co‐stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evalulated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three‐color flow cytometry analysis for the following receptors HLA‐DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA‐DR molecules, co‐stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two‐color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA‐DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co‐stimulatory molecules.

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Anatomical Origin of Dendritic Cells Determines Their Life Span in Peripheral Lymph Nodes

Cited by 191 publications

References 42 publications

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

Critical Role for Activation of Antigen-Presenting Cells in Priming of Cytotoxic T Cell Responses After Vaccination with Virus-Like Particles

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

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