TY - JOUR
T1 - Macrophage I-A/I-E expression and macrophage-stimulating lymphokines in murine lupus
AU - Kofler, Reinhard
AU - Schreiber, Robert D.
AU - Dixon, Frank J.
AU - Theofilopoulos, Argyrios N.
N1 - Funding Information:
’ This is Publication No. 3 135-IMM from the Department of Immunology, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, Calif. 92037. This work was supported by National Institutes of Health Grants AM 3 1023-01 and CA 34120, U.S. Public Health Services Grants AI 17354 and AI 07007, and the Eli Lilly Research Laboratories. 2 Supported by a postdoctoral research exchange grant from the Max Kade Foundation, New York. On leave of absence from the Institute for General and Experimental Pathology, University of Innsbruck Medical School, Innsbruck, Austria.
PY - 1984/8
Y1 - 1984/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0021142361&partnerID=8YFLogxK
U2 - 10.1016/0008-8749(84)90133-3
DO - 10.1016/0008-8749(84)90133-3
M3 - Article
C2 - 6204780
AN - SCOPUS:0021142361
SN - 0008-8749
VL - 87
SP - 92
EP - 100
JO - Cellular Immunology
JF - Cellular Immunology
IS - 1
ER -