The cellular basis for immune interferon production in autoimmune MRL-Ipr/Ipr mice.
Disturbances in immune interferon (IFN gamma) activity have been implicated in the development of human systemic lupus erythematosus (SLE) and the spontaneous disease sustained by autoimmune-prone mice. We therefore investigated the cellular basis for IFN gamma production in MRL-Ipr/Ipr mice and examined the relationship between synthesis of interleukin 2 (IL 2) and IFN gamma. In vitro IL 2 and IFN gamma production in 3 to 6-mo-old, autoimmune MRL-Ipr/Ipr and MRL-+/+ mice was compared with that seen in age- and sex-matched, immunologically normal CBA/J mice. 5 X 10(6) spleen cells were pulsed with 5 micrograms of concanavalin A (Con A), and the cellfree supernatant was assayed for IL 2 and IFN gamma activity at various times up to 72 hr. We found that peak levels of IL 2 in MRL mice were less than 10% of those in the CBA/J. Yet, production of IFN gamma by cells from the autoimmune and normal strains was quite comparable. The addition of murine IL 2 to optimally Con A-stimulated cells from the MRL-Ipr/Ipr or normal mice did not affect the subsequent peak production of IFN gamma. Although the primary producers of IFN gamma in cultures of normal mice bear the Lyt-2+ phenotype, the Lyt-1+2- T-cell subset was found to be the principal source of IFN gamma in the aged MRL-Ipr/Ipr. These data suggest that Lyt-1+ cells from MRL-Ipr/Ipr mice may be differentially responsive to the signal delivered by the same mitogenic lectin with respect to lymphokine production and may indicate a distorted commitment of such cells toward production of IFN gamma and repression of IL 2 synthesis. The relationship between hypoproduction of IL 2, this usual source of IFN gamma, and the autoimmune disease sustained by MRL-Ipr/Ipr mice remains unclear.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains / Q000276:immunology*; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology
D007376:Interleukin-2; D003208:Concanavalin A; D007371:Interferon-gamma