Stress proteins (HSP) and chemical-induced autoimmunity.
Various environmental and iatrogenic chemicals have been implicated in the induction of autoimmune responses and biomarkers for identification of such chemicals are imperative. The present study was initiated to examine whether induction of stress protein (HSP) synthesis is a common effect of immunoactive chemicals. This would be interesting because HSP-induction could result in the presentation of HSP-derived T cell epitopes, and recognition of these epitopes by HSP-reactive T cells could facilitate the initiation of (auto)immune responses. Such a role for HSP would clarify early aspects of chemical induction of immune responses and could provide a valuable biomarker for the identification of potentially immunoactive chemicals. It was found that of eight immunoactive chemicals, only HgCl2, dinitrochlorobenzene, and dibutyltin dichloride induced synthesis of HSC73/HSP72 and HSP90 in murine splenocytes in vitro. The induction by HgCl2 was identical in splenocytes from mice susceptible or not for Hg-induced autoimmunity. Following footpad injection of HgCl2, but not diphenylhydantoin, a marginal induction of HSC73 and possibly HSP72 but not HSP90 was found to precede the chemical-induced lymphoproliferation in draining lymph nodes of BALB/c mice. Finally, using stimulation of the IgG1 response to TNP-ficoll as a model for non-antigen-linked, T cell-dependent B cell stimulation, it was found that stimulation of this response by chemicals is independent of HSP induction. From these results, we conclude that it is unlikely that HSP function as general initiating neoantigens in chemically induced autoimmune responses.
Albers
R
R
Section of Immunotoxicology, Research Institute of Toxicology, Utrecht University, The Netherlands.
van der Pijl
A
A
Bol
M
M
Seinen
W
W
Pieters
R
R
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects*; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009947:Organotin Compounds / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D004137:Dinitrochlorobenzene; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D009947:Organotin Compounds; D008627:Mercuric Chloride; C020735:dibutyldichlorotin