Macrophage I-A/I-E expression and macrophage-stimulating lymphokines in murine lupus.
Seeking common abnormalities in mice genetically predisposed to lupus-like autoimmune disease, we investigated (1) the ontogeny of Ia antigens (I-A/I-E) on the surfaces of resident peritoneal macrophages (rpM phi) of lupus and normal mice, (2) spontaneous and lectin-induced in vitro production of M phi-stimulating factors (interferon, IFN; M phi-activating factor, MAF; M phi-Ia-inducing/recruiting factor, MIRF), and (3) responses of rpM phi from such animals to Ia-inducing signals. Indirect immunofluorescence techniques showed that Ia+ rpM phi increased numerically during the life spans of MRL/Mp lpr/lpr, while no such increase was observed in age-matched non-lpr MRL/Mp +/+ or (MRL/Mp lpr/lpr X MRL/Mp +/+)F1 hybrid mice. However, neonatal thymectomy, which prevents lymphoproliferation and autoimmune disease in MRL/Mp lpr/lpr mice, had no effect on this enhanced M phi I-A/I-E expression. NZB mice developed a similar increase with age, whereas BXSB and (NZB X NZW)F1 lupus mice, like immunologically normal controls, had low numbers of I-A/I-E+ rpM phi. Cultured splenocytes of lupus mice, including those with high percentages of I-A/I-E+ rpM phi, did not spontaneously (in the absence of mitogens) elaborate MIRF, MAF, or IFN activity. Furthermore, concanavalin A-stimulated splenocytes from lupus mice, particularly strains with early autoimmune disease manifestations [MRL/Mp lpr/lpr, male BXSB, and female (NZB X NZW)F1] produced levels of these lymphokines that were lower than normal controls. MRL/Mp lpr/lpr and NZB rpM phi, when stimulated in vitro with the supernatant of a MIRF-producing T cell hybridoma, did not hyperrespond. Our study shows that increased I-A/I-E+ rpM phi occur in some, but not all, lupus mice and this increase does not correlate with increased spontaneous or mitogen-induced production of M phi-stimulating lymphokines nor with hyperresponsiveness to Ia-inducing signals.
D000375:Aging; D000818:Animals; D005260:Female; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D007372:Interferons / Q000096:biosynthesis / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis / Q000502:physiology*; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D008817:Mice, Mutant Strains
D000949:Histocompatibility Antigens Class II; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D007372:Interferons