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Heat Shock Protein 70 (HSP70) induces cytotoxicity of T-helper cells

Stress-inducible heat shock protein 70 (HSP70) has gained plenty of attention because of its potent adjuvant capability to induce antigen-specific CD8+ cytotoxic T-lymphocyte (CTL) and CD4+ T-helper cell (Th1) responses. In this study, we investigated the behavior of T-cell subsets stimulated with endotoxin-free recombinant HSP70 with respect to proliferation, cytokine expression, cytotoxicity against allogeneic B-lymphoblastoid cell line (B-LCL) and K562 cells as well as target-independent cytotoxicity.

CD4+ cells exhibited a strong increase in proliferation after stimulation with HSP70, with rates of up to 29%. In the presence of target cells, a 35-fold up-regulation of granzyme B mRNA was observed after stimulation of CD4+ T-helper cells with HSP70 in combination with IL-7, -12 and -15. The target cell-independent secretion of granzyme B by CD4+ cells was greatly augmented after stimulation with HSP70 plus IL-2 or IL-7, -12 and -15.

In this study, we have shown that HSP70 is capable of inducing a cytotoxic response of T-helper cells in the absence of LPS or any other PAMPs. The granzyme B secretion and the cytolytic activity of CD4+ T cells is induced in a target-independent way, whereas the cytotoxic activity of CD3+ and CD8+ T cells can be further enhanced in the presence of the target cells. Our data provide novel insights into the role of extracellular HSP70 on T-cell immune response concerning the induction of target-independent T-helper cell cytotoxicity.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figueiredo, C., Wittmann, M., Wang, D. et al. Heat Shock Protein 70 (HSP70) induces cytotoxicity of T-helper cells. Cell Commun Signal 7 (Suppl 1), A28 (2009).

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