title: Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity.
abstract: Heat shock proteins (HSP) are widely distributed and highly immunogenic molecules. A novel property reported here is that stimulation with HSP70 of CD8-enriched T cells derived from naive non-human primates caused a dose-dependent increase in concentrations of the beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha or MIP-1beta. However, the concentrations of these beta-chemokines were greatly increased when the CD8 T cells derived from HSP70-immunized non-human primates were stimulated with HSP70. HSP linked to peptides or proteins combined generation of beta-chemokines with an adjuvant function by enhancing specific T cell proliferative responses and IgG and IgA antibodies. The beta-chemokine and adjuvant functions were also elicited by topical mucosal administration of HSP linked to an antigen. We postulate that microbial HSP can stimulate beta-chemokine production which may be responsible for innate adjuvanticity, as was found in cells eluted from normal rectal mucosal tissue, and constitutes a significant component of the mucosal-associated lymphoid system. Furthermore, stimulation of innate immunity may drive adaptive immunity and account for the protective effects of HSP against tumors and viruses.
authors.affiliation: Department of Immunobiology, Guy's King's and St. Thomas' Hospitals, Medical and Dental School, London, GB. thomas.lehner@kcl.ac.uk
authors.forename: T
authors.initials: T
authors.lastname: Lehner
authors.forename: L A
authors.initials: LA
authors.lastname: Bergmeier
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Tao
authors.forename: M
authors.initials: M
authors.lastname: Sing
authors.forename: R
authors.initials: R
authors.lastname: Spallek
authors.forename: R
authors.initials: R
authors.lastname: van der Zee
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D019742:Chemokines, CC / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D007109:Immunity; D011323:Primates
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D000956:Antigens, Viral; D019742:Chemokines, CC; D018840:HSP70 Heat-Shock Proteins