title: Target cell specificity of immunosuppression in murine lymphocytes exposed to 1,4-bis[(2-aminoethyl)amino]-5,8-dihydroxy-9,10-anthracenedione dihydrochloride (AEAD).
abstract: Exposure of murine lymphocytes to the highly-substituted anthraquinone 1,4-bis[(2-aminoethyl)amino]-5,8-dihydroxy-9,10-anthracenedione dihydrochloride (AEAD) results in a profound suppression of cytotoxic T-lymphocyte function. This immunosuppression is confined to CTL induction and cannot be restored by addition of exogenous interleukin-2 (IL-2), suggesting a defect at the level of the cytotoxic T-lymphocyte precursor (CTLp) cell. Production of both IL-1 and IL-2 were normal, and responsiveness to IL-1 was unaltered, although lymphocytes displayed a reduced responsiveness to IL-2. Cell surface marker analysis demonstrated no changes in relative numbers of lymphoid cell subsets, implying functional rather than population changes. The ability to activate CTLp with lectins was markedly reduced, as was CTL induction in thymocytes lacking functional T-helper cells. These data suggest that CTL suppression following in vivo or in vitro exposure to AEAD is due primarily to a direct effect on the CTLp cell.
authors.affiliation: Department of Cellular and Molecular Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
authors.forename: R V
authors.initials: RV
authors.lastname: House
authors.forename: J H
authors.initials: JH
authors.lastname: Dean
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007165:Immunosuppression Therapy; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D051379:Mice; D008942:Mitoxantrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D007375:Interleukin-1; D007376:Interleukin-2; C043485:CL 232468; D008942:Mitoxantrone