Specific sensitization of Lyt-1+2- T cells to spleen cells modified by the drug D-penicillamine or a stereoisomer.
A mouse model for assessing the sensitization of T cells to the drug D-penicillamine (D-Pen) has been established. Mice were primed with D-Pen in vivo and the secondary response of specific T cells was measured in a proliferative assay in vitro. Priming was achieved by injecting either free D-Pen or, more effectively, D-Pen in complete Freund's adjuvant at the base of the tail. After 7 to 9 days, the draining lymph node cells (responder cells) were restimulated in vitro with syngeneic spleen cells that had been preincubated with D-Pen for 20 to 22 hr and washed (D-Pen-SC). The thiol (-SH) group of D-Pen was required for generating effective stimulator cells; other thiol compounds, however, or heavy metals (Hg, Au) were unable to generate cross-reacting stimulators on incubation with spleen cells. Although D-Pen-SC proved to be good stimulator cells, thymocytes and mouse erythrocytes, after having been preincubated with D-Pen, completely failed to stimulate. The proliferating responder cells were Lyt-1+2- T cells that were highly specific for D-Pen-SC and were even capable of distinguishing between the two stereoisomers D-Pen and L-Pen. The splenic T cells of recipient mice were effectively primed by injecting D-Pen-SC, but not free D-Pen, via the i.v. route. These findings indicate that D-Pen can act as a hapten for specific T cells when presented on the surface of appropriate stimulator cells. Conceivably, if D-Pen were able to generate effective stimulator cells in vivo, this could lead to T cell reactions comparable to those in the graft-vs-host reaction (GVHR). We discuss the possibility that the GVH-like adverse immunologic side-effects of D-Pen in patients may have a GVHR-like pathogenesis.
N
N
Nagata
U
U
Hurtenbach
E
E
Gleichmann
D000818:Animals; D000950:Antigens, Ly; D001789:Blood Group Antigens / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010396:Penicillamine / Q000494:pharmacology*; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D000950:Antigens, Ly; D001789:Blood Group Antigens; D000939:Epitopes; D013438:Sulfhydryl Compounds; D010396:Penicillamine