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

Abstract：

: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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Kofler R,Schreiber RD,Dixon FJ,Theofilopoulos AN

doi

10.1016/0008-8749(84)90133-3

subject

Has Abstract

pub_date

1984-08-01 00:00:00

pages

92-100

issue

eissn

0008-8749

issn

1090-2163

pii

0008-8749(84)90133-3

journal_volume

pub_type

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