scholarly journals T Cell Activation by Heat Shock Protein 70 Vaccine Requires TLR Signaling and Scavenger Receptor Expressed by Endothelial Cells-1

2009 ◽  
Vol 183 (5) ◽  
pp. 3092-3098 ◽  
Author(s):  
Jianlin Gong ◽  
Bangmin Zhu ◽  
Ayesha Murshid ◽  
Hideki Adachi ◽  
Baizheng Song ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
T Cell Activation ◽  
Heat Shock Protein 70 ◽  
Cell Activation ◽  
Scavenger Receptor ◽  
Tlr Signaling

scholarly journals Interaction of human heat shock protein 70 with tumor-associated peptides

2009 ◽  
Vol 390 (4) ◽  
Author(s):  
Maya J. Pandya ◽  
Henriette Bendz ◽  
Florian Manzenrieder ◽  
Elfriede Noessner ◽  
Horst Kessler ◽  
...  
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
T Cell Activation ◽  
Heat Shock Protein 70 ◽  
Cell Activation ◽  
Peptide Sequence ◽  
Antigenic Peptides ◽  
Human Hsp70

Abstract Molecular chaperones of the heat shock protein 70 (Hsp70) family play a crucial role in the presentation of exogenous antigenic peptides by antigen-presenting cells (APCs). In a combined biochemical and immunological approach, we characterize the biochemical interaction of tumor-associated peptides with human Hsp70 and show that the strength of this interaction determines the efficacy of immunological cross-presentation of the antigenic sequences by APCs. A fluorescein-labeled cytosolic mammalian Hsc70 binding peptide is shown to interact with human Hsp70 molecules with high affinity (Kd=0.58 μm at 25°C). Competition experiments demonstrate weaker binding by Hsp70 of antigenic peptides derived from the tumor-associated proteins tyrosinase (Kd=32 μm) and melanoma antigen recognized by T cells (MART-1) (Kd=2.4 μm). Adding a peptide sequence (pep70) with high Hsp70 binding affinity (Kd=0.04 μm) to the tumor-associated peptides enables them to strongly interact with Hsp70. Presentation of tumor-associated peptides by B cells resulting in T cell activation in vitro is enhanced by Hsp70 when the tumor-associated peptides contain the Hsp70 binding sequence. This observation has relevance for vaccine design, as augmented transfer of tumor-associated antigens to APCs is closely linked to the vaccine's efficacy of T cell stimulation.

scholarly journals Efficient Activation of Human T Cells of Both CD4 and CD8 Subsets by Urease-Deficient Recombinant Mycobacterium bovis BCG That Produced a Heat Shock Protein 70-M. tuberculosis-Derived Major Membrane Protein II Fusion Protein

2013 ◽  
Vol 21 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Tetsu Mukai ◽  
Yumiko Tsukamoto ◽  
Yumi Maeda ◽  
Toshiki Tamura ◽  
Masahiko Makino
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Membrane Protein ◽  
Heat Shock Protein ◽  
Fusion Protein ◽  
T Cell Activation ◽  
Heat Shock Protein 70 ◽  
Cell Activation ◽  
Content Type

ABSTRACTFor the purpose of obtainingMycobacterium bovisbacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed ofMycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8+T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8+T cells and perforin-producing effector CD8+T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive toin vitrosecondary stimulation with HSP70, MMP-II, andM. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challengedM. tuberculosismore efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.

scholarly journals Natural Killer and NK-Like T-Cell Activation in Colorectal Carcinoma Patients Treated with Autologous Tumor-Derived Heat Shock Protein 96

2005 ◽  
Vol 65 (9) ◽  
pp. 3942-3949 ◽  
Author(s):  
Lorenzo Pilla ◽  
Paola Squarcina ◽  
Jorgelina Coppa ◽  
Vincenzo Mazzaferro ◽  
Veronica Huber ◽  
...  
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Colorectal Carcinoma ◽  
Heat Shock Protein ◽  
Natural Killer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Autologous Tumor

Hansenula polymorpha expressed heat shock protein gp96 exerts potent T cell activation activity as an adjuvant

2011 ◽  
Vol 151 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Yang Li ◽  
Haolei Song ◽  
Jin Li ◽  
Yanzhong Wang ◽  
Xiaoli Yan ◽  
...  
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hansenula Polymorpha ◽  
Heat Shock Protein Gp96

scholarly journals Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease

2017 ◽  
Vol 85 (8) ◽  
Author(s):  
Lucia Trotta ◽  
Kathleen Weigt ◽  
Katina Schinnerling ◽  
Anika Geelhaar-Karsch ◽  
Gerrit Oelkers ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
T Cell Responses ◽  
Tropheryma Whipplei ◽  
Content Type ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei, the proportions of activated effector CD4+ T cells, determined as CD40L+ IFN-γ+, were significantly lower in patients with CWD than in healthy controls; CD8+ T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei-specific degranulation, although CD69+ IFN-γ+ CD8+ T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei-derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei-derived proteins may contribute to the pathogenesis of CWD.

scholarly journals Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro.

1990 ◽  
Vol 110 (5) ◽  
pp. 1757-1766 ◽  
Author(s):  
W Risau ◽  
B Engelhardt ◽  
H Wekerle
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ifn Gamma

The endothelial blood-brain barrier (BBB) has a critical role in controlling lymphocyte traffic into the central nervous system (CNS), both in physiological immunosurveillance, and in its pathological aberrations. The intercellular signals that possibly could induce lymphocytes to cross the BBB include immunogenic presentation of protein (auto-)antigens by BBB endothelia to circulating T lymphocytes. This concept has raised much, though controversial, attention. We approached this problem by analyzing in vitro immunospecific interactions between clonal rat T lymphocyte lines with syngeneic, stringently purified endothelial monolayer cultures from adult brain micro-vessels. The rat brain endothelia (RBE) were established from rat brain capillaries using double collagenase digestion, density gradient fractionation and selective cytolysis of contaminating pericytes by anti-Thy 1.1 antibodies and complement. Incubation with interferon-gamma in most of the brain-derived endothelial cells induced Ia-antigens in the cytoplasm and on the cell surface in some of the cells. Before the treatment, the cells were completely Ia-negative. Pericytes were unresponsive to IFN-gamma treatment. When confronted with syngeneic T cell lines specific for protein (auto-)antigens (e.g., ovalbumin and myelin basic protein, MBP), RBE were completely unable to induce antigen-specific proliferation of syngeneic T lymphocytes irrespective of pretreatment with IFN-gamma and of cell density. RBE were inert towards the T cells, and did not suppress T cell activation induced by other "professional" antigen presenting cells (APC) such as thymus-derived dendritic cells or macrophages. IFN-gamma-treated RBE were, however, susceptible to immunospecific T cell killing. They were lysed by MBP-specific T cells in the presence of the specific antigen or Con A. Antigen dependent lysis was restricted by the appropriate (MHC) class II product. We conclude that the interaction of brain endothelial cells with encephalitogenic T lymphocytes may involve recognition of antigen in the molecular context of relevant MHC products, but that this interaction per se is insufficient to initiate the full T cell activation program.

Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes

2009 ◽  
Vol 387 (2) ◽  
pp. 229-233 ◽  
Author(s):  
Rui Zhan ◽  
Xue Leng ◽  
Xiaohua Liu ◽  
Xinxing Wang ◽  
Jingbo Gong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Classical Pathway

scholarly journals Liver Sinusoidal Endothelial Cells Contribute to Hepatic Antigen-Presenting Cell Function and Th17 Expansion in Cirrhosis

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1227
Author(s):  
Esther Caparrós ◽  
Oriol Juanola ◽  
Isabel Gómez-Hurtado ◽  
Amaya Puig-Kroger ◽  
Paula Piñero ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Bile Duct ◽  
T Cell Activation ◽  
Cell Activation ◽  
Experimental Models ◽  
Cd4 T Cell ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Bacterial Peritonitis

Hepatic immune function is compromised during cirrhosis. This study investigated the immune features of liver sinusoidal endothelial cells (LSECs) in two experimental models of cirrhosis. Dendritic cells, hepatic macrophages, and LSECs were isolated from carbon tetrachloride and bile duct-ligated rats. Gene expression of innate receptors, bacterial internalization, co-stimulatory molecules induction, and CD4+ T cell activation and differentiation were evaluated. Induced bacterial peritonitis and norfloxacin protocols on cirrhotic rats were also carried out. LSECs demonstrated an active immunosurveillance profile, as shown by transcriptional modulation of different scavenger and cell-adhesion genes, and their contribution to bacterial internalization. LSECs significantly increased their expression of CD40 and CD80 and stimulated CD4+ T cell activation marker CD71 in both models. The pro-inflammatory Th17 subset was expanded in CCl4-derived LSECs co-cultures. In the bile duct ligation (BDL) model, CD4+ T cell differentiation only occurred under induced bacterial peritonitis conditions. Differentiated pro-inflammatory Th cells by LSECs in both experimental models were significantly reduced with norfloxacin treatment, whereas Foxp3 tolerogenic Th CD4+ cells were expanded. Conclusion: LSECs’ participation in the innate-adaptive immune progression, their ability to stimulate pro-inflammatory CD4+ T cells expansion during liver damage, and their target role in norfloxacin-induced immunomodulation granted a specific competence to this cell population in cirrhosis.

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