The role of heat shock protein (hsp70) in dendritic cell maturation: Hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors

Kuppner, M. C.; Gastpar, Robert; Gelwer, Svetlana; Nößner, Elfriede; Ochmann, Oswin; Scharner, Anabel; Issels, Rolf D.

doi:10.1002/1521-4141(200105)31:5<1602::aid-immu1602>3.0.co;2-w

Cited by 193 publications

(114 citation statements)

References 29 publications

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“…As mentioned above, HSP themselves can stimulate the maturation of APC and the production of proinflammatory cytokines [10,30,31], and the HSP effect has to be carefully distinguished from effects of contaminations like LPS [32,33]. In our experiments, complexing Hsp70 with the antigenic peptide was crucial for an enhanced proliferation of CD4 + T cells.…”

Section: Discussionmentioning

confidence: 70%

“…Different mechanisms explaining the effect of HSP have been discussed, including an increased uptake and enhanced intracellular processing of chaperoned peptide by APC [18,28,29], a direct effect of HSP on APC [6, 10,[29][30][31] or an effect only due to microbial contaminations of the HSP preparation [32,33]. HSP:peptide complexes can be released by necrotic cells [2] and taken up by APC via specific receptors (reviewed in [34]).…”

Section: Discussionmentioning

confidence: 99%

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The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

et al. 2005

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Heat shock proteins (HSP) can interact with a wide variety of peptides and the resulting HSP:peptide complexes are known to be highly immunogenic. The ability of HSP:peptide complexes to elicit CD8 + T cell responses by cross-presentation of exogenous antigen via MHC class I is well known. In contrast, their role in the activation of CD4 + T cells is less clearly defined, although several recent studies in mice and T cell lines suggest an involvement of HSP in the presentation of antigenic peptides via MHC class II. In this study we have investigated the potential of antigenic peptides from tetanus toxin and influenza hemagglutinin complexed to the human stress-inducible Hsp70 to enhance activation and proliferation of human memory CD4 + T cells. Hsp70:peptide complexes were found to amplify the proliferation of antigen-specific CD4 + T cells as confirmed by HLA-DR tetramer staining. Complex formation of the antigenic peptide with Hsp70 was absolutely required to elicit an antigen-specific amplification. This effect was most pronounced at low doses of antigen and decreasing APC/CD4 + T cell ratios. Taken together, we show the potential of Hsp70 to enhance antigen-specific CD4 + T cell proliferation and to increase the immunogenicity of presented peptides in human CD4 + T cells.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

et al. 2005

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“…Among these activities the stimulation of macrophages to secrete cytokines and the activation of antigen-presenting and costimulatory molecules on dendritic cells (Basu et al 2000;Singh-Jasuja et al 2000;Kuppner et al 2001), the in vivo maturation and migration of CD11c ϩ (Binder et al 2000a), and the activation of T cells (Breloer et al 1999) are worth mentioning. All these effects are produced through specific interactions with surface receptors on target cells (Arnold-Schild et al 1999;Binder et al 2000b;Castellino et al 2000;Sondermann et al 2000).…”

Section: Discussionmentioning

confidence: 99%

The heat shock proteins, Hsp70 and Hsp83, of Leishmania infantum are mitogens for mouse B cells

Rico¹,

Gironès²,

Fresno³

et al. 2002

Cell Stress Chaper

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Extending earlier studies, this report demonstrates that Leishmania infantum heat shock proteins (Hsps), Hsp70 and Hsp83, expressed as recombinant proteins fused to the Escherichia coli maltose-binding protein (MBP), are potent mitogens for murine splenocytes. The response was not due to lipopolysaccharide (LPS) because the stimulatory activity of Hsp preparations was sensitive to boiling and trypsin treatments, whereas the corresponding activity of LPS was resistant to both treatments. It was found that in vitro incubation of spleen cells with the Leishmania Hsps leads to the expansion of CD220-bearing populations, suggesting a direct effect of these proteins on B lymphocytes. In fact, splenocytes from B cell-deficient mice did not proliferate in response to the Leishmania Hsps. In contrast, spleen cells from athymic nude mice were significantly stimulated by these recombinant proteins as an indication that the MBP-Hsp70 and MBP-Hsp83 recombinant proteins behave as T cell-independent mitogens of B cells. Furthermore, both proteins were able to induce proliferation on B cell populations purified from BALB/c spleen.

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“…HSP70 has been reported to activate the innate immune response, resulting in the maturation of DCs, [13][14][15] the upregulation of proinflammatory cytokines [13][14][15][16] and nitric oxide release by APCs. 17 Rapid intracellular Ca 2 þ flux 18 and CD14-dependent toll-like receptor (TLR) 2-and TLR4-mediated activation of the MyD88/interleukin-1 receptor associated kinase (IRAK)/nuclear factor (NF)-kappaB signal transduction pathway 18,19 have been reported as consequences of HSP70 binding to cell surface receptors on APCs.…”

Section: Introductionmentioning

confidence: 99%

Secretory heat-shock protein as a dendritic cell-targeting molecule: a new strategy to enhance the potency of genetic vaccines

Shen

et al. 2004

Gene Ther

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DNA vaccines are an appealing strategy for inducing cytotoxic T-lymphocyte and antibody responses against tumor cells as well as infectious agents. Dendritic cells (DCs) play a critical role in inducing immune responses, but their potential is not fully utilized in the DNA vaccine setting since they take up only a minor fraction of the injected DNA. Here we describe a novel DNA vaccination strategy based on the targeting of a modified tumor-associated antigen, the human papilloma virus (HPV) type 16 E7 protein, to DCs by a heat-shock protein (HSP) to enhance antigen presentation and immune responses. Specifically, a chimerical HPV-E7 and HSP70 fusion gene preceded with a leader sequence was constructed. When mice were immunized with this construct, the DNA is taken up by various types of cells, which then produce and secrete an HPV-E7-HSP70 fusion protein that is targeted to DCs by the HSP70 portion of the chimerical molecule for antigen presentation. In studies to test the efficacy of this strategy, we demonstrated that DNA vaccination with this secretory HPV-E7-HSP70 construct strongly enhanced an antigen-specific CD8 þ T-cell response as well as a specific B-cell response in mice. Furthermore, this immunization approach not only protected mice against lethal challenge with an HPV E7-expressing tumor line (TC-1), but also showed a therapeutic effect against established tumors. The results of this study indicate that secretory HSPs can be broadly used to target tumorassociated antigens to DCs to enhance antigen-specific immune responses. Gene Therapy (2004) 11, 924-932.

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The role of heat shock protein (hsp70) in dendritic cell maturation: Hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors

Cited by 193 publications

References 29 publications

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

The heat shock proteins, Hsp70 and Hsp83, of Leishmania infantum are mitogens for mouse B cells

Secretory heat-shock protein as a dendritic cell-targeting molecule: a new strategy to enhance the potency of genetic vaccines

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