Heat shock protein 70 (HSP70) induces cytotoxicity of T-helper cells.
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.
Figueiredo
Constança
C
Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
Wittmann
Miriam
M
Wang
Dong
D
Dressel
Ralf
R
Seltsam
Axel
A
Blasczyk
Rainer
R
Eiz-Vesper
Britta
B
D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000502:physiology; D004768:Enterotoxins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology* / Q000502:physiology*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D020014:K562 Cells / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D017252:CD3 Complex; D004768:Enterotoxins; D005456:Fluorescent Dyes; D018840:HSP70 Heat-Shock Proteins; D019409:Interleukin-15; D007376:Interleukin-2; D011994:Recombinant Proteins; C031818:enterotoxin B, staphylococcal; D053804:Granzymes