Heat shock protein 70(HSP70) induces cytotoxicity of T-helper cells

Abstract

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 gran-zyme B was observed after stimulation of CD4+ T cells with HSP70 in combination with interleukin-7(IL-7)/IL-12/IL-15. The target cell-independent secretion of gran-zyme B by CD4+ cells was greatly augmented after stimulation with HSP70 plus IL-2 or IL-7/IL-12/IL-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 are induced in a target-independent way, whereas the cy-totoxic 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. © 2009 by The American Society of Hematology.