STRESS PROTEINS (HSP) AND CHEMICAL-INDUCED AUTOIMMUNITY

Various environmental and iatrogenic chemicals have been implicated in the induction of autoimmune responses and biomarkers for identificati on of such chemicals are imperative, The present study was initiated t o examine whether induction of stress protein (HSP) synthesis is a com mon effect of immunoactive chemicals. This would be interesting becaus e HSP-induction could result in the presentation of HSP-derived T cell epitopes, and recognition of these epitopes by HSP-reactive T cells c ould facilitate the initiation of (auto)immune responses. Such a role for HSP would clarify early aspects of chemical induction of immune re sponses and could provide a valuable biomarker for the identification of potentially immunoactive chemicals, It was found that of eight immu noactive chemicals, only HgCl2, dinitrochlorobenzene, and dibutyltin d ichloride induced synthesis of HSC73/HSP72 and HSP90 in murine splenoc ytes in vitro. The induction by HgCl2 was identical in splenocytes fro m mice susceptible or not for Hg-induced autoimmunity. Following footp ad injection of HgCl2, but not diphenylhydantoin, a marginal induction of HSC73 and possibly HSP72 but not HSP90 was found to precede the ch emical-induced lymphoproliferation in draining lymph nodes of BALB/c m ice. Finally, using stimulation of the IgG(1) response to TNP-ficoll a s a model for non-antigen-linked, T cell-dependent B cell stimulation, it was found that stimulation of this response by chemicals is indepe ndent of HSP induction. From these results, we conclude that it is unl ikely that HSP function as general initiating neoantigens in chemicall y induced autoimmune responses. (C) 1996 Academic Press, Inc.