title: Analysis of retinoid-mediated immunosuppression in vivo. Effects of Ro23-6457 on cellular alloimmune responses.
abstract: We have investigated the immunosuppressive effects of a synthetic retinoid, Ro23-6457, on the in vivo development of cellular alloimmunity. We initially observed that treatment of C57B1/6 mice with 10 mg/kg/day Ro23-6457 drug could prolong the survival of DBA/2 cardiac allografts, thus verifying its immunosuppressive potential in murine experimental models. We next used the sponge matrix model of allograft rejection and limiting dilution analysis (LDA) of cytotoxic T lymphocyte (CTL) frequency to dissect this phenomenon further. In this experimental system we observed the following effects of Ro23-6457: (1) dose-dependent decrease in the number of LDA-detectable, donor-reactive CTL accumulating in sponge matrix allografts; (2) failure to interfere with in vitro assays of cellular alloimmunity, including LDA; and (3) antigen non-specific depression of LDA-detectable CTL in lymph nodes, spleen and especially in peripheral blood. For peripheral blood CTL, the drug eliminated LDA-detectable CTL, an effect that was reversible and could not be attributed to the activation of suppressor cells. Since Ro23-6457 has little effect on the number of peripheral blood Thy1.2+ cells, it appears that this drug does not physically eliminate CTL, but makes them temporarily hyporesponsive to antigen stimulation, and thus undetectable in functional assays like LDA.
authors.affiliation: Department of Surgery, Ohio State University College of Medicine, Columbus 43210.
authors.forename: C G
authors.initials: CG
authors.lastname: Orosz
authors.forename: N E
authors.initials: NE
authors.lastname: Zinn
authors.forename: D K
authors.initials: DK
authors.lastname: Bishop
authors.forename: D L
authors.initials: DL
authors.lastname: Leppink
authors.forename: D
authors.initials: D
authors.lastname: Faherty
authors.forename: R M
authors.initials: RM
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D016027:Heart Transplantation; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014184:Transplantation, Homologous / Q000276:immunology; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; C061340:Ro 23-6457; D014212:Tretinoin