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Rapid Generation Of Broad T-Cell Immunity In Humans After A Single Injection Of Mature Dendritic Cells, Madhav V. Dhodapkar, Ralph M. Steinman, Mark Sapp Jan 1999

Rapid Generation Of Broad T-Cell Immunity In Humans After A Single Injection Of Mature Dendritic Cells, Madhav V. Dhodapkar, Ralph M. Steinman, Mark Sapp

Publications

Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201- positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4+ T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific …


Vaccination With Mage-3a1 Peptide-Pulsed Nature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells And Induces Regression Of Some Metastases In Advanced Stage Iv Melanoma, Beatrice Thurner, Ina Haendle, Claudia Röder Jan 1999

Vaccination With Mage-3a1 Peptide-Pulsed Nature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells And Induces Regression Of Some Metastases In Advanced Stage Iv Melanoma, Beatrice Thurner, Ina Haendle, Claudia Röder

Publications

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigens, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 x 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 106 and 12 x 106 DCs, respectively. Only minor (less than …


Differentiation Of Phagocytic Monocytes Into Lymph Node Dendritic Cells In Vivo, Gwendalyn J. Randolph, Kayo Inaba, Davide E. Robbiani Jan 1999

Differentiation Of Phagocytic Monocytes Into Lymph Node Dendritic Cells In Vivo, Gwendalyn J. Randolph, Kayo Inaba, Davide E. Robbiani

Publications

We investigated the differentiation and trafficking of inflammatory monocytes that phagocytosed subcutaneously injected fluorescent microspheres. As expected, most of the monocytes became microsphere+ macrophages, which remained in subcutaneous tissue. However, about 25% of latex+ cells migrated to the T cell area of draining lymph nodes, where they expressed dendritic cell (DC)-restricted markers and high levels of costimulatory molecules. Microsphere-transporting cells were distinct from resident skin DCs, and this transport was reduced by more than 85% in monocyte-deficient osteopetrotic mice. Thus, a substantial minority of inflammatory monocytes carry phagocytosed particles to lymph nodes and differentiate into DCs


Virus Replication Begins In Dendritic Cells During The Transmission Of Hiv-1 From Mature Dendritic Cells To T Cells, Angela Granelli-Piperno, Victoria Finkel, Elena Delgado, Ralph M. Steinman Jan 1999

Virus Replication Begins In Dendritic Cells During The Transmission Of Hiv-1 From Mature Dendritic Cells To T Cells, Angela Granelli-Piperno, Victoria Finkel, Elena Delgado, Ralph M. Steinman

Publications

Background: To initiate immunity, dendritic cells (DCs) capture antigens or viruses at body surfaces, undergo maturation to express T-cell costimulatory molecules, and then migrate to lymphoid organs. DCs at body surfaces can capture human immunodeficiency virus 1 (HIV-1), but mature DCs do not support replication of the virus unless T cells are added. The initial site for HIV-1 replication remains unknown and it is unclear whether replication can take place in DCs or whether the virus must first be transmitted from DCs to T cells. Results: We generated mature DCs from monocyte precursors. Upon infection with HIV-1, reverse transcription was …


Trance, A Tumor Necrosis Factor Family Member Critical For Cd40 Ligand- Independent T Helper Cell Activation, Martin F. Bachmann, Brian R. Wong, Régis Josien Jan 1999

Trance, A Tumor Necrosis Factor Family Member Critical For Cd40 Ligand- Independent T Helper Cell Activation, Martin F. Bachmann, Brian R. Wong, Régis Josien

Publications

CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4+ T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4+ T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4+ T cell responses that produce normal levels of interferon γ, suggesting a CD40L/CD40-independent mechanism of CD4+ T cell priming that to date has not been elucidated. Here we …