期刊
BLOOD
卷 113, 期 13, 页码 3008-3016出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-06-162727
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- Deutsche Jose Carreras Leukamie Stiftung
- Deutsche Forschungsgemeinschaft [DFG Wi1822/5-1]
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 interleukin-7 (IL-7)/IL-12/IL-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/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 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. (Blood. 2009; 113: 3008-3016)
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