Heat Shock Protein 70 Inhibits Caspase-Dependent and -Independent Apoptosis in Jurkat T Cells

2000 ◽  
Vol 257 (1) ◽  
pp. 58-66 ◽  
Author(s):  
E.M. Creagh ◽  
R.J. Carmody ◽  
T.G. Cotter
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Jurkat T Cells

scholarly journals Flagellin Contamination of Recombinant Heat Shock Protein 70 Is Responsible for Its Activity on T Cells

2006 ◽  
Vol 282 (7) ◽  
pp. 4479-4484 ◽  
Author(s):  
Zhiyong Ye ◽  
Yunn-Hwen Gan
Keyword(s):  
Escherichia Coli ◽  
T Cells ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Burkholderia Pseudomallei ◽  
Jurkat T Cells ◽  
Recombinant Hsp70 ◽  
Shock Proteins

Heat shock proteins (Hsp) 60 and 70 have been intensively studied for their ability to activate innate immunity. Heat shock proteins had been shown to induce the activation of dendritic cells, T cells, and B cells. However, the possible contamination of endotoxin in heat shock protein preparations makes their function as an activator of immune system ambiguous. Here, we examined the ability of bacterial Hsp60 and Hsp70 to activate Jurkat T cells and primary T cells. We found that Burkholderia pseudomallei Hsp70 and Mycobacterium tuberculosis Hsp70 could costimulate Jurkat T cells to make IL-2 and signal through TLR5. This costimulatory activity is not due to endotoxin or contaminants signaling via TLR2 nor TLR4. However, recombinant Hsp70 expressed in Escherichia coli ΔfliC strain completely lost its ability to costimulate T cells. Thus, the activation of T cells by recombinant Hsp70 is ascribed to flagellin contamination.

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.

Heat shock protein 70 (Hsp70) interacts with the Notch1 intracellular domain and contributes to the activity of Notch signaling in myelin-reactive CD4 T cells

2015 ◽  
Vol 287 ◽  
pp. 19-26 ◽  
Author(s):  
Maciej Juryńczyk ◽  
Przemysław Lewkowicz ◽  
Małgorzata Domowicz ◽  
Marcin P. Mycko ◽  
Krzysztof W. Selmaj
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Notch Signaling ◽  
Cd4 T Cells ◽  
Heat Shock Protein 70 ◽  
Intracellular Domain

scholarly journals The Adjuvant Effects of Mycobacterium tuberculosis Heat Shock Protein 70 Result from the Rapid and Prolonged Activation of Antigen-Specific CD8+ T Cells In Vivo

2002 ◽  
Vol 169 (10) ◽  
pp. 5622-5629 ◽  
Author(s):  
Lisa A. E. Harmala ◽  
Elizabeth G. Ingulli ◽  
Julie M. Curtsinger ◽  
Michelle M. Lucido ◽  
Clint S. Schmidt ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cd8 T Cells ◽  
Heat Shock Protein 70 ◽  
Adjuvant Effects

Heat shock protein 70 binds caspase-activated DNase and enhances its activity in TCR-stimulated T cells

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1788-1796 ◽  
Author(s):  
Qing-Li Liu ◽  
Hiroyuki Kishi ◽  
Kenzo Ohtsuka ◽  
Atsushi Muraguchi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Dna Fragmentation ◽  
Heat Shock Protein 70 ◽  
Peptide Binding ◽  
Binding Domain ◽  
Free System ◽  
Caspase Activated Dnase

AbstractDNA fragmentation is a hallmark of cells undergoing apoptosis and is mediated mainly by the caspase-activated DNase (CAD or DNA-fragmentation factor 40 [DFF40]), which is activated when released from its inhibitor protein (ICAD or DFF45) upon apoptosis signals. Here we analyzed the effect of heat shock protein 70 (Hsp70) on CAD activity in T-cell receptor (TCR)–induced apoptosis using a T-cell line (TAg-Jurkat). Overexpression of Hsp70 significantly augmented the apoptotic cell death as well as DNA fragmentation in CD3/CD28- or staurosporine-stimulated cells. Following stimulation of cells with CD3/CD28 or staurosporine, Hsp70 was coprecipitated with free CAD, but not with CAD associated with ICAD. Furthermore, the purified Hsp70 dose-dependently augmented DNA-fragmentation activity of caspase-3–activated CAD in a cell-free system. Peptide-binding domain–deleted Hsp70 could neither bind nor augment its activity, while adenosine triphosphate (ATP)–binding domain–deleted Hsp70 or the peptide-binding domain itself bound CAD and augmented its activity. These results indicate that the the binding of Hsp70 to the activated CAD via the peptide-binding domain augments its activity. Although CAD lost its activity in an hour after being released from ICAD in vitro, its activity was retained after an hour of incubation in the presence of Hsp70, suggesting that Hsp70 may be involved in stabilization of CAD activity. Finally, CAD that had been coprecipitated with Hsp70 from the cell lysate of staurosporine-activated 293T cells induced chromatin DNA fragmentation and its activity was not inhibited by ICAD. These results suggest that Hsp70 binds free CAD in TCR-stimulated T cells to stabilize and augment its activity.

scholarly journals Inducible Heat Shock Protein 70 Reduces T Cell Responses and Stimulatory Capacity of Monocyte-derived Dendritic Cells

2012 ◽  
Vol 287 (15) ◽  
pp. 12387-12394 ◽  
Author(s):  
Pawel Stocki ◽  
Xiao N. Wang ◽  
Anne M. Dickinson
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
T Cell Responses ◽  
Inflammatory Reactions ◽  
Cell Responses ◽  
Immature Dendritic Cells

Heat shock protein 70 (Hsp70) has gained a lot of attention in the past decade due to its potential immunoregulatory functions. Some of the described proinflammatory functions of Hsp70 became controversial as they were based on recombinant Hsp70 proteins specimens, which were later shown to be endotoxin-contaminated. In this study we used low endotoxin inducible Hsp70 (also known as Hsp72, HSPA1A), and we observed that after a 24-h incubation of monocyte-derived immature dendritic cells (mo-iDCs) with 20 μg/ml of low endotoxin Hsp70, their ability to stimulate allogenic T cells was reduced. Interestingly, low endotoxin Hsp70 also significantly reduced T cell responses when they were simulated with either IL-2 or phytohemagglutinin, therefore showing that Hsp70 could alter T cell responses independently from its effect on mo-iDCs. We also reported a greater response of Hsp70 treatment when activated versus nonactivated T cells were used. This effect of Hsp70 was similar for all tested populations of T cells that included CD3+, CD4+, or CD8+. Taken together, our observations strongly suggest that Hsp70 might dampen, rather than provoke, T cell-mediated inflammatory reactions in many clinical conditions where up-regulation of Hsp70 is observed.

scholarly journals Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation

2016 ◽  
Vol 310 (7) ◽  
pp. C568-C575 ◽  
Author(s):  
Rachel A. Rigg ◽  
Laura D. Healy ◽  
Marie S. Nowak ◽  
Jérémy Mallet ◽  
Marisa L. D. Thierheimer ◽  
...  
Keyword(s):  
T Cells ◽  
Platelet Aggregation ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Platelet Activation ◽  
Whole Blood ◽  
Heat Shock Protein 70 ◽  
Ex Vivo ◽  
Granule Secretion ◽  
And Function

Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological function. Recent studies have reported roles for specific chaperone activities in blood platelets in maintaining hemostasis; however, the functions of Hsp70 in platelet physiology remain uninvestigated. Here we characterize roles for Hsp70 activity in platelet activation and function. In vitro biochemical, microscopy, flow cytometry, and aggregometry assays of platelet function, as well as ex vivo analyses of platelet aggregate formation in whole blood under shear, were carried out under Hsp70-inhibited conditions. Inhibition of platelet Hsp70 blocked platelet aggregation and granule secretion in response to collagen-related peptide (CRP), which engages the immunoreceptor tyrosine-based activation motif-bearing collagen receptor glycoprotein VI (GPVI)-Fc receptor-γ chain complex. Hsp70 inhibition also reduced platelet integrin-αIIbβ3activation downstream of GPVI, as Hsp70-inhibited platelets showed reduced PAC-1 and fibrinogen binding. Ex vivo, pharmacological inhibition of Hsp70 in human whole blood prevented the formation of platelet aggregates on collagen under shear. Biochemical studies supported a role for Hsp70 in maintaining the assembly of the linker for activation of T cells signalosome, which couples GPVI-initiated signaling to integrin activation, secretion, and platelet function. Together, our results suggest that Hsp70 regulates platelet activation and function by supporting linker for activation of T cells-associated signaling events downstream of platelet GPVI engagement, suggesting a role for Hsp70 in the intracellular organization of signaling systems that mediate platelet secretion, “inside-out” activation of platelet integrin-αIIbβ3, platelet-platelet aggregation, and, ultimately, hemostatic plug and thrombus formation.

scholarly journals Expression of heat shock protein 70 blocks thymic differentiation of T cells in transgenic mice

Immunology ◽  
1998 ◽  
Vol 95 (4) ◽  
pp. 559-565 ◽  
Author(s):  
LEE ◽  
PARK ◽  
KIM ◽  
PARK ◽  
KIM ◽  
...  
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Transgenic Mice ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70
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