Macrophage I-A/I-E expression and macrophage-stimulating lymphokines in murine lupus

Reinhard Kofler, Robert D. Schreiber, Frank J. Dixon, Argyrios N. Theofilopoulos

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36 Scopus citations


Seeking common abnormalities in mice genetically predisposed to lupus-like autoimmune disease, we investigated (1) the ontogeny of la antigens (I-A/I-E) on the surfaces of resident peritoneal macrophages (rpMφ) of lupus and normal mice, (2) spontaneous and lectin-induced in vitro production of Mφ-stimulating factors (interferon, IFN; Mφ-activating factor, MAF; Mφ-Ia-inducing/recruiting factor, MIRF), and (3) responses of rpMφ from such animals to lainducing signals. Indirect immunofluorescence techniques showed that Ia+ rpMφ increased numerically during the life spans of MRL/Mp lpr/lpr, while no such increase was observed in agematched non-lpr MRL/Mp +/+ or (MRL/Mp lpr/lpr × 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 Mφ I-A/I-E expression. NZB mice developed a similar increase with age, whereas BXSB and (NZB × NZW)F1 lupus mice, like immunologically normal controls, had low numbers of I-A/I-E+ rpMφ. Cultured splenocytes of lupus mice, including those with high percentages of I-A/I-E+ rpMφ, 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 × NZW)F1] produced levels of these lymphokines that were lower than normal controls. MRL/Mp lpr/lpr and NZB rpMφ, 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+ rpMφ occur in some, but not all, lupus mice and this increase does not correlate with increased spontaneous or mitogen-induced production of Mφ-stimulating lymphokines nor with hyperresponsiveness to Ia-inducing signals.

Original languageEnglish
Pages (from-to)92-100
Number of pages9
JournalCellular Immunology
Issue number1
StatePublished - Aug 1984


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