CpG oligonucleotides induce strong humoral but only weak CD4+ T cell responses to protein antigens in rhesus macaques in vivo

Vaccine ◽  
2005 ◽  
Vol 23 (25) ◽  
pp. 3310-3317 ◽  
Author(s):  
Gunther Hartmann ◽  
Anja Marschner ◽  
Pablo Renner Viveros ◽  
Christiane Stahl-Hennig ◽  
Martin Eisenblätter ◽  
...  
Keyword(s):  
T Cell ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Protein Antigens ◽  
Cell Responses ◽  
Cpg Oligonucleotides

scholarly journals TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand–independent T Helper Cell Activation

1999 ◽  
Vol 189 (7) ◽  
pp. 1025-1031 ◽  
Author(s):  
Martin F. Bachmann ◽  
Brian R. Wong ◽  
Régis Josien ◽  
Ralph M. Steinman ◽  
Annette Oxenius ◽  
...  
Keyword(s):  
T Cell ◽  
Family Member ◽  
T Cell Responses ◽  
Cd40 Ligand ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
T Cell Priming ◽  
Deficient Mice ◽  
Necrosis Factor

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 show that CD4+ T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4+ T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4+ T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention.

scholarly journals In Vivo Suppression of Naive CD4 T Cell Responses by IL-2- and Antigen-Stimulated T Lymphocytes in the Absence of APC Competition

2008 ◽  
Vol 181 (5) ◽  
pp. 3323-3335 ◽  
Author(s):  
Hiroto Inaba ◽  
Meredith Steeves ◽  
Phuong Nguyen ◽  
Terrence L. Geiger
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+and CXCR5−CD4 T Cell Responses in Rhesus Macaques

2015 ◽  
Vol 195 (3) ◽  
pp. 994-1005 ◽  
Author(s):  
Smita S. Iyer ◽  
Sailaja Gangadhara ◽  
Blandine Victor ◽  
Rosy Gomez ◽  
Rahul Basu ◽  
...  
Keyword(s):  
T Cell ◽  
Envelope Protein ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals Deciphering the Mechanisms of Improved Immunogenicity of Hypochlorous Acid-Treated Antigens in Anti-Cancer Dendritic Cell-Based Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 271
Author(s):  
Michele Graciotti ◽  
Fabio Marino ◽  
HuiSong Pak ◽  
Petra Baumgaertner ◽  
Anne-Christine Thierry ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Hypochlorous Acid ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Tumor Lysate ◽  
Cell Responses ◽  
Significant Difference

Hypochlorous acid (HOCl)-treated whole tumor cell lysates (Ox-L) have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic cell (DC)-based vaccines, improving downstream immune responses both in vitro and in vivo. However, the mechanisms behind the improved immunogenicity are still elusive. To address this question, we conducted a proteomic and immunopeptidomics analyses to map modifications and alterations introduced by HOCl treatment using a human melanoma cell line as a model system. First, we show that one-hour HOCl incubation readily induces extensive protein oxidation, mitochondrial biogenesis, and increased expression of chaperones and antioxidant proteins, all features indicative of an activation of oxidative stress-response pathways. Characterization of the DC proteome after loading with HOCl treated tumor lysate (Ox-L) showed no significant difference compared to loading with untreated whole tumor lysate (FT-L). On the other hand, detailed immunopeptidomic analyses on monocyte-derived DCs (mo-DCs) revealed a great increase in human leukocyte antigen class II (HLA-II) presentation in mo-DCs loaded with Ox-L compared to the FT-L control. Further, 2026 HLA-II ligands uniquely presented on Ox-L-loaded mo-DCs were identified. In comparison, identities and intensities of HLA class I (HLA-I) ligands were overall comparable. We found that HLA-II ligands uniquely presented by DCs loaded with Ox-L were more solvent exposed in the structures of their source proteins, contrary to what has been hypothesized so far. Analyses from a phase I clinical trial showed that vaccinating patients using autologous Ox-L as an antigen source efficiently induces polyfunctional vaccine-specific CD4+ T cell responses. Hence, these results suggest that the increased immunogenicity of Ox-L is, at least in part, due to qualitative and quantitative changes in the HLA-II ligandome, potentially leading to an increased HLA-II dependent stimulation of the T cell compartment (i.e., CD4+ T cell responses). These results further contribute to the development of more effective and immunogenic DC-based vaccines and to the molecular understanding of the mechanism behind HOCl adjuvant properties.

Distinct in vivo CD8 and CD4 T cell responses against normal and malignant tissues

2012 ◽  
Vol 62 (1) ◽  
pp. 101-112 ◽  
Author(s):  
David Coe ◽  
Caroline Addey ◽  
Matthew White ◽  
Nida Harwood ◽  
Julian Dyson ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals CD4+ T-cell responses among adults and young children in response to Streptococcus pneumoniae and Haemophilus influenzae vaccine candidate protein antigens

Vaccine ◽  
2013 ◽  
Vol 31 (30) ◽  
pp. 3090-3097 ◽  
Author(s):  
Sharad K. Sharma ◽  
David Roumanes ◽  
Anthony Almudevar ◽  
Tim R. Mosmann ◽  
Michael E. Pichichero
Keyword(s):  
Streptococcus Pneumoniae ◽  
T Cell ◽  
Young Children ◽  
Haemophilus Influenzae ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Protein Antigens ◽  
Cell Responses ◽  
Candidate Protein

Immature dendritic cells induce alternative CD4+ T-cell responses in vivo

2001 ◽  
Vol 33 (1-2) ◽  
pp. 240 ◽  
Author(s):  
R.M. Suri ◽  
N. Kukutsch ◽  
S. Fowler ◽  
F. Powrie ◽  
J. Austyn
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Immature Dendritic Cells

Optimization of intracellular cytokine staining for the quantitation of antigen-specific CD4+ T cell responses in rhesus macaques

2004 ◽  
Vol 288 (1-2) ◽  
pp. 61-79 ◽  
Author(s):  
Marie-Claire Gauduin ◽  
Amitinder Kaur ◽  
Shabbir Ahmad ◽  
Tilahun Yilma ◽  
Jeffrey D. Lifson ◽  
...  
Keyword(s):  
T Cell ◽  
Rhesus Macaques ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Intracellular Cytokine ◽  
Cell Responses
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