Submitted June 16, 2008
Accepted November 2, 2008
Heat shock protein 70 (HSP70) induces cytotoxicity of T-helper cells
Constanca Figueiredo, Miriam Wittmann, Dong Wang, Ralf Dressel, Axel Seltsam, Rainer Blasczyk, and Britta Eiz-Vesper*
Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany
Department of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany
Department of Cellular and Molecular Immunology, University of Goettingen, Goettingen, Germany
* Corresponding author; email: eiz-vesper.britta{at}mh-hannover.de.
Heat shock protein 70 (HSP70) has gained plenty of attention because of its adjuvant capability to induce CD8+ cytotoxic T lymphocyte and CD4+ T-helper cell responses. We investigated the behavior of T-cell subsets stimulated with endotoxin-free HSP70 with respect to proliferation, cytokine expression, cytotoxicity against allogeneic B-lymphoblastoid cell line and K562 cells as well as target-independent cytotoxicity. CD4+ cells exhibited a strong increase in proliferation after stimulation with HSP70 (29%). In the presence of targets, a 35-fold up-regulation of granzyme B was observed after stimulation of CD4+ T cells with HSP70 in combination with IL-7/-12/-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/-15. In this study, we showed that HSP70 is capable of inducing a cytotoxic response of T-helper cells in the absence of lipopolysaccharide. The granzyme B secretion and cytolytic activity of T helper 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 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.
