THE AUTOIMMUNOGENIC CHEMICALS HGCL2 AND DIPHENYLHYDANTOIN STIMULATE IGG PRODUCTION TO TNP-FICOLL AND TNP-OVA, SUPPORTING AND EXTENDING THE GRAFT-VERSUS-HOST HYPOTHESIS FOR CHEMICAL INDUCTION OF AUTOIMMUNITY

Bypass of T-cell tolerance via non-cognate graft-versus-host (GVH)-lik e help from T-helper (Th) cells activated by chemically altered or ind uced epitopes, has been postulated as a mechanism underlying chemical induction of autoimmunity. To functionally test this hypothesis, we as sessed whether the autoimmunogenic chemicals HgCl2 and diphenylhydanto in (DPH), like GVH reactions, stimulate specific immunoglobulin G (IgG ) responses to trinitrophenyl (TNP)-Ficoll but not to TNP-ovalbumin. I gG responses were quantified in the popliteal lymph node by enzyme-lin ked immunosorbent spot-forming cell assay (ELISPOT) assays 7 days afte r s.c. injection of antigens, parental cells, chemicals or combination s thereof into the footpad of semiallogeneic Fl mice. Antigens, chemic als, or cells alone induced few TNP-specific IgG antibody-forming cell (AFC) compared with untreated mice. Co-injection of parental cells or chemicals with TNP-Ficoll stimulated the TNP-specific response per ly mph node similar to 50- and similar to 40-fold, respectively. In contr ast, the Ige response to TNP-ovalbumin could not be stimulated by GVH reactions, whereas HgCl2 and DPH dose-dependently increased this respo nse up to similar to 25- and similar to 250-fold, respectively. Howeve r, responses to TNP-ovalbumin pre-incubated with HgCl2 or DPH could be stimulated similar to 6-8 fold by GVH reactions. Observed similar adj uvanticity of chemicals and parental cells for TNP-Ficoll support a GV H-like action of autoimmunogenic chemicals. In addition, the chemicals modify TNP-ovalbumin such that B cells recognizing this antigen becom e susceptible to non-cognate stimulation by GVH reactions.