Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity

Heat shock proteins (HSP) are widely distributed and highly immunogenic mol ecules; A novel property reported here is that stimulation with HSP70 of CD 8-enriched T cells derived from naive non-human primates caused a dose-depe ndent increase in concentrations of the beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha or MIP-1 beta. However, the concentratio ns of these beta-chemokines were greatly increased when the CD8 T cells der ived from HSP70-immunized non-human primates were stimulated with HSP70. HS P linked to peptides or proteins combined generation of beta-chemokines wit h 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 antige n. We postulate that microbial HSP can stimulate beta-chemokine production which may be responsible for innate adjuvanticity,as was found in cells elu ted from normal rectal mucosal tissue, and constitutes a significant compon ent 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.