Immunity to D-penicillamine: genetic, cellular, and chemical requirements for induction of popliteal lymph node enlargement in the mouse.
- 15 July 1987
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 139 (2), 411-416
- https://doi.org/10.4049/jimmunol.139.2.411
Abstract
To elucidate the pathogenesis of immunological diseases induced by the drug D-Penicillamine (D-Pen) the requirements for sensitization to this drug were investigated. Mice were subcutaneously (s.c.) injected into one hind footpad with a solution of D-Pen without adjuvant, and reactivity to D-Pen was determined in the popliteal lymph node assay (PLNA) by weight increase of the draining PLN, the incorporation of 3H-thymidine, and trapping of 51Cr-labeled syngeneic lymphocytes in the draining PLN. The peak of the primary PLN response was obtained between day 7 and 10 after injecting 1 mg of D-Pen per mouse. Likewise, PLN enlargement could be induced by injecting 18 hr nonadherent spleen cells s.c. that had been pretreated overnight with D-Pen in vitro. D-Pen-induced PLN enlargement was primarily caused by cell proliferation within the lymph node, and only a minor portion was due to trapping of circulating lymphocytes. The majority of the cells in the enlarged PLN were B cells; T cells, however, were required for generation of PLN enlargement. For induction of PLN reactivity to D-Pen, the stereoisomer L-Pen, and the dimer D-Pen disulfide, it was mandatory that the respective molecules were administered in ionized form. PLN reactivity to D-Pen is controlled by at least two loci, one mapping to the I region, possibly A beta A alpha, the other(s) to the non-H-2 background. As far as studied, high responsiveness was inherited dominantly. The PLN reaction proved to be antigen-specific, since D-Pen-primed mice exhibited an enhanced reaction when challenged with a suboptimal dose of D-Pen, but not when challenged with an unrelated drug, diphenylhydantoin (DPH). The possible relationship between immunity to D-Pen and autoimmunity induced by this drug is discussed.This publication has 4 references indexed in Scilit:
- Mercuric chloride-, gold sodium thiomalate-, and d-penicillamine-induced antinuclear antibodies in miceToxicology and Applied Pharmacology, 1986
- Effects of prolonged administration of d-penicillamine or captopril in various strains of ratsClinical Immunology and Immunopathology, 1984
- Selective action of D-penicillamine on guinea pig peritoneal macrophage Fcγ receptors for homologous, monomeric IgG1Immunology Letters, 1983
- Systemic Lupus Erythematosus During Penicillamine Therapy for Rheumatoid ArthritisAnnals of Internal Medicine, 1982