Immunization with heat shock protein 70 from methylcholanthrene-induced sarcomas induces tumor protection correlating with in vitro T cell responses

2002 ◽  
Vol 51 (3) ◽  
pp. 163-170 ◽  
Author(s):  
Anne-Marie T. Ciupitu ◽  
Max Petersson ◽  
Koji Kono ◽  
Jehad Charo ◽  
Rolf Kiessling
2017 ◽  
Vol 85 (8) ◽  
Author(s):  
Lucia Trotta ◽  
Kathleen Weigt ◽  
Katina Schinnerling ◽  
Anika Geelhaar-Karsch ◽  
Gerrit Oelkers ◽  
...  

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.


2012 ◽  
Vol 287 (15) ◽  
pp. 12387-12394 ◽  
Author(s):  
Pawel Stocki ◽  
Xiao N. Wang ◽  
Anne M. Dickinson

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.


2011 ◽  
Vol 70 (Suppl 2) ◽  
pp. A44-A45 ◽  
Author(s):  
E. Koffeman ◽  
E. Elst ◽  
F. van Wijk ◽  
B. Prakken ◽  
A. van Royen-Kerkhof

2009 ◽  
Vol 390 (4) ◽  
Author(s):  
Maya J. Pandya ◽  
Henriette Bendz ◽  
Florian Manzenrieder ◽  
Elfriede Noessner ◽  
Horst Kessler ◽  
...  

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.


1999 ◽  
Vol 70 (1-2) ◽  
pp. 105-115 ◽  
Author(s):  
A.P Koets ◽  
V.P.M.G Rutten ◽  
A Hoek ◽  
D Bakker ◽  
F van Zijderveld ◽  
...  

1997 ◽  
Vol 56 ◽  
pp. 379
Author(s):  
H. Direskeneli ◽  
E. Ekşioǧlu-Demiralp ◽  
T. Ergun ◽  
T. Lehner ◽  
T. Akoǧlu

1998 ◽  
Vol 10 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Ruurd van der Zee ◽  
Stephen M. Anderton ◽  
A.Berent J. Prakken ◽  
A.G.A.Liesbeth Paul ◽  
Willem van Eden

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