RESUMEN
We describe a new, spontaneously occurring BALB/c-derived murine T-cell leukemia. The leukemic cells, designated LB, grow rapidly and progressively in the syngeneic host with no signs of effective immunological resistance. LB cells expressed the Thy-1+, Lyt-2+, L3T4-, CD3- class-I+, CD25+ (IL-2 receptor, IL-2R), class-II-, gp70- phenotype. As LB cells express IL-2, as indicated by staining with 2 distinct anti-CD25 IL-2R monoclonal antibodies (MAbs), the therapeutic efficacy of IL-2-diphtheria toxin-related protein was tested on this leukemic model. IL-2-diphtheria toxin, but not diphtheria toxin, efficiently inhibited the proliferation of LB cells. The proliferation of a murine myeloma cell line, which does not express IL-2R, was not inhibited by IL-2-diphtheria toxin. The possible implantation of this animal model in fundamental and practical studies is discussed.
Asunto(s)
Modelos Animales de Enfermedad , Leucemia de Células T/inmunología , Receptores de Interleucina-2/inmunología , Animales , Anticuerpos Monoclonales , División Celular , Línea Celular/patología , Separación Celular , Toxina Diftérica/uso terapéutico , Evaluación Preclínica de Medicamentos , Femenino , Citometría de Flujo , Humanos , Interleucina-2/uso terapéutico , Leucemia de Células T/patología , Leucemia de Células T/terapia , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes de Fusión/uso terapéutico , Células Tumorales Cultivadas/patologíaRESUMEN
Mice of 1.5, 9, 22, and 31 to 32 months of age were injected with the thymus-dependent antigen, TNP-SRC, or the thymus-independent antigen, TNP-SRC, TNP-MRC. The anti-SRC and TNP immune responses to TNP-SRC were markedly reduced in older mice, whereas the anti-TNP response to the TNP-MRC showed no substantial decline. Young mice produced higher anti-TNP plaque-forming cell responses after injection of TNP-SRC than after TNP-MRC, whereas in older mice the reverse obtained. Old mice but not young mice displayed a high anti-SRC cross-reactive response after injection of TNP-MRC. The avidity of anti-TNP antibody of young mice immunized with TNP-SRC was higher than that following immunization with TNP-MRC, whereas the avidities of anti-TNP antibodies from old mice injected with these two reagents were the same. Those individual mice which showed a poorly regulated immune response also displayed an autologous anti-MRC plaque-forming cell response after injection of either TNP-SRC or TNP-MRC. It is suggested that mechanisms mediated by suppressor T cells may be responsible for regulating the autoimmune response to modified self antigens, and that these are severely impaired in age individuals.