Increased activation and altered ratio of interferon-gamma: interleukin-4 secreting cells in MRL-lpr/lpr mice.
Cytokine specific ELIspot assays were used to monitor the number of cells secreting IL-4 and IFN gamma in MRL-lpr/lpr mice of different ages. The cytokine repertoire expressed by MRL-lpr/lpr mice was skewed towards the over-production of IFN gamma (and away from IL-4) when compared to that of MRL-+/-/+/- and BALB/c mice. With increasing age and disease severity, the ratio of IFN gamma: IL-4 secreting cells rose in MRL-lpr/lpr mice but decreased in normal animals. This changing ratio of IFN gamma: IL-4 secreting cells correlated with changes in the ratio of IgG2a: IgG1 secreting cells in these mice. Our findings suggest that cytokine secreting CD4+ and CD8+ cells are hyperactivated in young MRL-lpr/lpr mice, and that disease progression is associated with a disruption in the normal ratio of Th1:Th2 production in vivo.
Shirai
A
A
Division of Viral Products, CBER/FDA, Bethesda, MD 20892, USA.
Conover
J
J
Klinman
D M
DM
D000367:Age Factors; D000375:Aging; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003208:Concanavalin A / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma