Dendritic Cells: From Ignored Cells to Major Players in T-Cell-Mediated Immunity

Schuler, Gerold; Thurner, Beatrice; Romani, Nikolaus

doi:10.1159/000237474

Cited by 66 publications

(35 citation statements)

References 30 publications

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“…Immunotherapy through T cell vaccination or vaccination with dendritic cells is regarded as a promising strategy for the treatment of various tumor entities such as malignant melanomas [11][12][13][14][15][16] , and high expectations have been placed on cytokine-modulated immunotherapies for hepatic tumors [17,18] . It is well known that RFA can induce an unspecific immune stimulation [4] .…”

Section: Discussionmentioning

confidence: 99%

Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

Hänsler

Wissniowski²,

Schuppan³

et al. 2006

WJG

115

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to 0.109 (± 0.005) for CD4 + and 0.11 (± 0.012) for CD8 + T cells against HCC, and to 0.115 (± 0.031) for CD4 + and 0.15 (± 0.02) for CD8 + cells for colorectal metastases (P < 0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respective cancer cells was low with 2.62 (± 0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was < 2% of maximum release in all experiments. CONCLUSION:Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8 + T cells after RFA. INTRODUCTIONOpen surgery is still the gold standard for the treatment of hepatocellular carcinoma (HCC) and liver metastases of colorectal cancer. However, more than 75% of these patients are non-resectable for various reasons, such as size and location of the tumor. Radio-frequency thermal ablation (RFA) is a common therapy option for unresectable liver tumors. Thus it was shown that RFA and laserinduced thermo-therapy (LiTT) can achieve survival times comparable to surgery in selected patients [1][2][3] . RFA uses a radio-frequency current to induce coagulation necrosis which results in a local thermal necrosis accompanied by Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases www

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Section: Discussionmentioning

confidence: 99%

Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

Hänsler

Wissniowski²,

Schuppan³

et al. 2006

WJG

115

View full text Add to dashboard Cite

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“…It seems not to be important for priming immune responses because it requires Abs of high affinity, which are themselves the result of an immune response. Thus, the Fc⑀RI is thought to be involved in the amplification of ongoing immune responses, such as allergy (32,63). The outcome of T cell stimulation might vary if the presentation by DC were to be performed with varying contributions from Fc⑀RI (55).…”

Section: Discussionmentioning

confidence: 99%

T Cell Reactivity with Allergoids: Influence of the Type of APC

Kahlert

Grage-Griebenow

Stüwe

et al. 2000

The Journal of Immunology

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The use of allergoids for allergen-specific immunotherapy has been established for many years. The characteristic features of these chemically modified allergens are their strongly reduced IgE binding activity compared with the native form and the retained immunogenicity. T cell reactivity of chemically modified allergens is documented in animals, but in humans indirect evidence of reactivity has been concluded from the induction of allergen-specific IgG during immunotherapy. Direct evidence of T cell reactivity was obtained recently using isolated human T cells. To obtain further insight into the mechanism of action of allergoids, we compared the Ag-presenting capacity of different APC types, including DC and macrophages, generated from CD14+ precursor cells from the blood of grass pollen allergic subjects, autologous PBMC, and B cells. These APC were used in experiments together with Phl p 5-specific T cell clones under stimulation with grass pollen allergen extract, rPhl p 5b, and the respective allergoids. Using DC and macrophages, allergoids exhibited a pronounced and reproducible T cell-stimulating capacity. Responses were superior to those with PBMC, and isolated B cells failed to present allergoids. Considerable IL-12 production was observed only when using the DC for Ag presentation of both allergens and allergoids. The amount of IL-10 in supernatants was dependent on the phenotype of the respective T cell clone. High IL-10 production was associated with suppressed IL-12 production from the DC in most cases. In conclusion, the reactivity of Th cells with allergoids is dependent on the type of the APC.

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“…It seems likely that IgE/FcεRI–mediated mechanisms are involved or dominate the antigen uptake and presentation by PBMC from allergic subjects, and thus allergoids with their strongly reduced IgE binding have a clear disadvantage. In contrast DC can take up antigen very effectively by pinocytosis [32, 51, 53, 54]. Obviously antigen uptake by this nonspecific mechanism accommodates both allergen and allergoid, and allergoids may be at an advantage due to their denatured native conformation.…”

Section: Discussionmentioning

confidence: 99%

Reactivity of T Cells with Grass Pollen Allergen Extract and Allergoid

Kähler¹,

Stüwe²,

Cromwell³

et al. 1999

Int Arch Allergy Immunol

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Background: Successful allergen–specific immunotherapy is achieved with progressively increasing doses of allergen or allergoid. In order to gain further insight into the mechanism of action of allergoids several in vitro investigations were conducted. Methods: Peripheral blood mononuclear cells (PBMC) from grass pollen allergic and nonallergic subjects were stimulated with either grass pollen extract or allergoid and the proliferation and cytokine production (IL–5, IFN–γ) were measured. Similar investigations were performed with Phl p 5–specific T cell lines (TCL) and clones (TCC). Dendritic cells and PBMC were compared in terms of their relative efficacies as antigen–presenting cells. Results: Both allergen and allergoid induced proliferation and Th2 and Th1 cytokine synthesis by PBMC of allergic subjects, whereas PBMC of nonallergic subjects did not produce IL–5. The maximum level of IL–5 was obtained with a lower concentration than was necessary for maximal IFN–γ production. Higher stimulation doses of allergen and allergoid shifted the cytokine profiles towards a Th1 phenotype. TCL and TCC clearly showed reactivity with both allergen and allergoid when using autologous PBMC for antigen presentation, but compared with the native allergen the reactivity of the allergoid was reduced with most of the TCC. Using dendritic cells for antigen presentation a pronounced increase of stimulation of the TCC especially for the allergoids becomes obvious. Conclusion: In common with grass pollen allergen the corresponding allergoids possess a strong allergen–specific T cell–stimulating capacity. However, the degree of T cell stimulation by the allergoid seems to be dependent on the type of the antigen–presenting cell. Both, allergen and allergoid, can modulate T cell responses in a dose–dependent manner.

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Dendritic Cells: From Ignored Cells to Major Players in T-Cell-Mediated Immunity

Cited by 66 publications

References 30 publications

Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

T Cell Reactivity with Allergoids: Influence of the Type of APC

Reactivity of T Cells with Grass Pollen Allergen Extract and Allergoid

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