title: Concomitant administration of hapten and IL-2-toxin (DAB486-IL-2) results in specific deletion of antigen-activated T cell clones.
abstract: During the proliferative burst after Ag recognition, T cells express cell-surface, high-affinity IL-2R. The importance of IL-2R+ T cells in supporting/mediating tissue injury has been documented by the ability of mAb anti-IL2R therapies to prevent allograft rejection and autoimmunity. The delayed-type hypersensitivity (DTH) response, an experimental model of T-dependent immunity, offers the possibility of studying responses mounted against defined Ag. We previously reported that the chimeric IL-2 toxin (DAB486-IL-2) prevents DTH responses and selectively eliminates activated IL-2R bearing CD4 and CD8 T cells from lymph nodes draining the site of inflammation. We have examined the duration of immunosuppression and relative specificity of action of DAB486-IL-2 and anti-CD3 mAb for Ag-activated clones in a murine model of DTH using two different noncross-reacting haptens. Treatment with DAB486-IL-2 generates a state of selective unresponsiveness to subsequent challenge with the hapten introduced during the therapeutic period. Immediately after cessation of DAB486-IL-2 therapy, immunization with an unrelated hapten induces a normal vigorous immune response. By comparison, anti-CD3 mAb treatment causes a broad immunosuppression because unrelated haptens introduced after anti-CD3 therapy do not evoke a vigorous immune response. After cessation of DAB486-IL-2 toxin treatment response to the hapten is eventually restored probably by cells trafficking from the thymus, because thymectomized hosts remain unresponsive to the hapten. Taken together these data reinforce the role of the IL-2R as an important target for immunosuppression in T cell-mediated immune reactions. DAB-486-IL-2 treatment confers highly selective immunosuppression.
authors: Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA 02115.
authors: M G
authors: MG
authors: Bastos
authors: O
authors: O
authors: Pankewycz
authors: V E
authors: VE
authors: Rubin-Kelley
authors: J R
authors: JR
authors: Murphy
authors: T B
authors: TB
authors: Strom
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002999:Clone Cells; D004167:Diphtheria Toxin / Q000494:pharmacology; D006241:Haptens / Q000276:immunology*; D007108:Immune Tolerance; D000922:Immunotoxins / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004167:Diphtheria Toxin; D006241:Haptens; D000922:Immunotoxins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2