Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The age-dependent capacity of NZB and (NZB x NZW)F1 hybrid, BALB/c, DBA/2, C57BL/6 and C3H mice to generate T cell-mediated immune responses was assessed qualitatively and quantitatively by measuring the following effector functions: (a) the time course of alloreactive cytotoxic T-cell activity triggered in vitro was comparable for NZ and other mouse strains; cell reactivity generated in vivo against EL4 tumour cells was low in young (NZB x NZW)F1 mice and in DBA/2 mice but was comparable for older (NZB x NZW)F1, NZB and other mouse strains; (b) the time-dependent, vaccinia virus-specific, cytotoxic T-cell activity after systemic infection was similar for all mouse strains; (c) the T cell-dependent primary footpad swelling after local injection with lymphocytic choriomeningitis virus was within the same range for all mouse strains tested with respect to size and kinetics of the reaction; (d) the cell-mediated immune protection against Listeria monocytogenes after systemic infection revealed that NZ mice are, independent of age, more susceptible than C3H or C57BL/6 mice and comparable to A strain mice. Therefore, these responses in young, or clinically relatively normal older, NZB or (NZB x NZW)F1 strains that are affected by a lupus-like autoimmune disease did not differ markedly from the range of responses of other mouse strains of 2-14 months of age, which are not known to be similarly diseased. Thus, overall cell-mediated immunity of NZ mice as assessed quantitatively and kinetically in these functional models is within normal ranges. Possible T-cell defects may therefore be selective and either do not occur or were not detected in these models.
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PMID:Comparison of T cell-mediated immune responsiveness of NZB, (NZB x &NZW)F1 hybrid and other murine strains. 14 94

Early in life, mice of four kinds [NZB, (NZB X NZW)F1, MRL/1, and male BXSB] with autoimmune disease spontaneously produced far more (greater than 3 S.D.) anti-hapten antibody-forming cells in spleens and greater concentrations of anti-hapten antibodies in sera than immunologically normal strains of mice (AKR, BALB/c, C57BL/6, DBA/1-J, DBA/2J, LG/J, 129, NZW, and female BXSB). This increased nonspecific antibody production by the abnormal animals' B cells correlated well with the spontaneous development of anti-single-stranded DNA antibodies, but not with serum levels of the viral envelope glycoprotein, gp70. These results suggest that the spontaneous formation of autoantibodies in mice whose immunologic disorder is manifested by a lupus-like disease may result from polyclonal activation of B cells by endogenous or exogenous B cell activators.
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PMID:Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. 36 41

Renal lesions at the chronic phase of MHC class-II-disparate graft-versus-host reaction (GVHR) were examined. To induce GVHR, C57BL/6 (B6) spleen cells were injected twice into either (B6 x bm12)F1 (class-II-disparate), (B6 x bm1)F1 (class-I-disparate) or (bm1 x bm12)F1 mice (class-I + II-disparate). For comparison, (C57BL/10 x DBA/2)F1 (BDF1) mice injected with DBA/2 spleen cells were also used. (B6 x bm12)F1 and BDF1 recipients showed marked elevation of anti-DNA antibodies, circulating immune complexes (CIC) and the number of immunoglobulin producing cells (IgPC). At 20 weeks after cell injection, severe immune complex glomerulonephritis (ICGN) was observed in (B6 x bm12)F1 recipients, but was far less severe in (bm1 x bm12)F1 recipients and was not observed in (B6 x bm1)F1 recipients. ICGN was also observed in BDF1 recipients at 12 weeks after cell injection. By immunofluorescent microscopy, IC deposition was detected along the capillary loops and also in the mesangial area in (B6 x bm12)F1 recipients, while BDF1 recipients showed only a capillary pattern. By light microscopy, the renal lesion of (B6 x bm12)F1 recipients appeared similar to those of BDF1 recipients. Histologically, (B6 x bm12)F1 recipients serve as a good model for lupus glomerulonephritis induced by class-II-disparate GVHR.
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PMID:Histological characteristics of lupus nephritis in F1 mice with chronic graft-versus-host reaction across MHC class II difference. 161 13

Induction of a graft-versus-host (GVH) reaction (GVHR) in non-irradiated (C57BL/10ScSn x DBA/2)F1 mice (BDF1) with DBA/2 lymphoid cells leads to chronic GVH disease (GVHD). One of the pathological alterations of this type of GVHD is hyperplasia of host B cells with production of lupus-like autoantibodies. This hyperstimulation of host B cells has previously been demonstrated to be induced by alloreactive donor T helper cells that were also proposed to maintain it. We provide three pieces of experimental evidence in support of this concept. First, treatment of mice with chronic GVHD by injection of monoclonal anti-Thy-1.2 antibodies, performed at week 6 after the injection of C57BL/6 lymphoid cells into (C57BL/6 x C57BL.bm12)F1 mice led to a significant decrease in the titre of anti-nuclear antibodies. Second, CD4+ donor T cells persisted in BDF1 mice with GVHD (GVHF1) for at least 10 weeks after the induction of GVHR; these T cells showed alloreactive helper activity against H-2b MHC determinants of the opposite parent in vitro. Third, T cells of GVHF1 mice, obtained 2 months after the induction of GVHR and transferred into normal secondary recipients, induced signs of chronic GVHD in DBF1 but not in DBA/2 mice. The combined results show that persisting donor T helper cells in GVHF1 mice retain their alloreactivity towards H-2 class II antigens for a long time after the induction of GVHR and they strongly suggest that these T cells are also the driving force behind the production of lupus-like autoantibodies at the late stage of chronic GVHD.
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PMID:Persistence of allospecific helper T cells is required for maintaining autoantibody formation in lupus-like graft-versus-host disease. 214 86

The present studies dealt with the pathogenesis of renal involvement in murine chronic graft-versus-host disease, which is a model for human systemic lupus erythematosus. The disease was induced in (C57BL10xDBA/2)F1 hybrids by injection of DBA/2 lymphocytes. The animals developed systemic disease accompanied by deposition of autoantibodies in the glomeruli and a lupus type of nephritis. Antibodies were eluted from glomeruli isolated during various stages of the disease by magnetic extraction from iron-perfused kidneys. For assessment of the specificity of the antibodies, we used indirect immunofluorescence, an enzyme-linked immunosorbent assay, and immunoblotting. In glomeruli from week 4, autoantibodies were found to be directed against several antigens, among which were the glomerular basement membrane component laminin and the glomerular enzyme dipeptidyl peptidase IV, whereas week 8 glomeruli also showed antibodies directed against nuclear antigens. Both laminin and dipeptidyl peptidase IV are known nephritogenic antigens occurring in renal tubular epithelial brush border preparations. Antibodies eluted from isolated glomeruli of diseased animals bound in a granular pattern along the glomerular capillary wall after in vivo transfer. Anti-renal tubular epithelial antibodies in the sera of diseased animals were affinity purified and injected into naive mice, which induced immune complex glomerulonephritis and proteinuria, thus confirming the nephritogenic role of these autoantibodies in this model.
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PMID:Characterization and in vivo transfer of nephritogenic autoantibodies directed against dipeptidyl peptidase IV and laminin in experimental lupus nephritis. 239 30

In addition to a lupus-like syndrome and massive T cell proliferation, MRL-lpr/lpr(MRL/l) mice develop an arthritic process very similar serologically and histologically to human rheumatoid arthritis (RA). Recently, we have developed in DBA/1 mice an experimental model of autoimmune arthritis (EAA) which shares clinical features with RA, by injecting homologous type II collagen (CII). In order to investigate the possible relationship between the spontaneous polyarthritis of MRL/l mice and collagen induced EAA, we immunized MRL/l mice with mouse (M) CII. Our findings revealed that the injection of 100 micrograms M-CII in young or old MRL/l mice did not modify the articular pathology which spontaneously develops in non-injected mice. Circulating autoantibodies to native M-CII were found in the sera of immunized young mice but were not detected in non injected or immunized old mice. Conversely, denatured alpha 1 (II) chains or CB peptides derived from M-CII were recognized by most of the MRL/l sera whether mice had been immunized or not. The incidence of positive sera as well as the intensity of the response evaluated by Western blot analysis increased with the age of the mice. Taken together, our data suggest that, even if the injection of homologous CII in MRL/l mice may accelerate the onset of joint pathology, the spontaneous disease arises independently of an autoimmune response against native CII.
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PMID:Polyarthritis in MRL-lpr/lpr mice: mouse type II collagen is antigenic but not arthritogenic. 249 40

These experiments examined the effects of genes outside of the H-2 region on disease susceptibility and pathogenesis. Four strains of mice with the susceptible H-2 type, H-2d, but different non-H-2 genes were studied. B10, D2, Balb/c, NZB, and DBA/2J mice were injected with 4 mg of apoferritin i.p. q.d. for 28 days. B10, D2 and Balb/c mice developed proliferative and crescentic glomerulonephritis. NZB mice developed proliferative and crescentic glomerulonephritis with wire loop lesions suggestive of lupus. DBA/2J mice developed only minimal mesangial proliferation without crescents or necrosis. Electron microscopy showed subepithelial and mesangial deposits in B10, D2, moderate subepithelial and mesangial deposits in Balb/c, and marked mesangial, subendothelial and subepithelial deposits in NZB. Immunofluorescence demonstrated the presence of IgG, IgM, C3 and apoferritin in these deposits. The DBA/2J mice had only minimal mesangial deposits by immunofluorescence and electron microscopy. These experiments demonstrate that non-H-2 genes alter the H-2d determined disease susceptibility seen in H-2 congenic mice. NZB genes can alter the disease so that lupus-like lesions develop and DBA/2J genes can substantially ameliorate the disease.
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PMID:Non-H-2 genes alter the H-2 determined susceptibilities in immune complex nephritis. 253 Mar 82

These studies explore the regulation of immunoglobulin production in autoimmune mice. B cells were transferred from normal or autoimmune mice into H-2 compatible xid recipients. When transferred to autoimmune-prone xid mice, cells from either donor produced significant levels of autoantibody. Cells from the same animals transferred to normal xid recipients produced little autoantibody. An ELISA spot assay was then used to study the development of B cell repertoires in autoimmune animals. Young lupus-prone mice developed repertoires in which B cells reactive with both conventional antigens and autoantigens were simulated to a similar degree, a finding consistent with the influence of polyclonal B cell activation. To examine the effect of exogenously administered immune activators on the development of B cell repertoires, normal DBA/2 mice were stimulated with LPS or goat anti-mouse IgD. This led to a quantitative increase in the number of Ig-secreting cells and expression of a repertoire similar to that present in autoimmune mice. Immunization with a specific antigen induced a repertoire skewed toward reactivity against that antigen which did not resemble that present in autoimmune mice. These findings are consistent with the view that polyclonal activation contributes to the production of autoantibodies in early murine lupus.
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PMID:Regulation of B cell activation in autoimmune mice. 279 46

The inoculation of B6D2F1 mice with T lymphocytes from the C57BL/6 parental strain induces an "immunosuppressive" graft-vs-host reaction (B6 GVH), whereas inoculation of T cells from the other, DBA/2 parental strain induces an "immunostimulatory" GVH reaction and a lupus-like disease (DBA GVH). The present study compares cytotoxic T lymphocyte (CTL) function in the spleens of these GVH mice as well as differences in the donor inoculum that could account for these different types of GVH. We observed that the B6 GVH induces an immunodeficiency that encompasses CTL precursors (and possibly T helper cells) and results in suppressor cells that abrogate responses to both trinitrophenyl (TNP)-modified self and third party alloantigens. In contrast, the DBA GVH induces only a T helper cell immunodeficiency and results in suppressor cells selective for class II restricted L3T4+ T helper cells. Chimeric T cells were detected in both types of GVH. In the B6 GVH both L3T4+ and Lyt-2+ donor cells were observed, although Lyt-2+ cells predominated. In the DBA GVH, donor T cells were almost exclusively of the L3T4+ phenotype. The lack of appreciable donor Lyt-2+ cells in the DBA GVH can be explained by a defect in the DBA donor inoculum manifested by a naturally occurring two-fold reduction in Lyt-2+ cell numbers as well as a nine-fold reduction in CTL precursors with anti-F1 specificity. T cells in the DBA inoculum, therefore, are predominantly L3T4+. A similar defect induced in B6 donor cells by anti-Lyt2 antibody and complement not only converted the suppressive GVH to a stimulatory GVH, as measured by anti-DNA antibodies, but also resulted in a T cell immune deficiency characteristic of the DBA GVH, i.e., a selective loss of the TNP-self CTL response. Thus the presence or absence of adequate numbers of functioning Lyt-2+ cells in the donor inoculum is correlated with the development of either a suppressive or stimulatory GVH, respectively. That donor Lyt-2+ cells mediate a suppressive GVH through cytolytic mechanisms is evidenced by greater than 70% reduction in B6 GVH spleen cell numbers and readily demonstrable anti-F1 CTL activity by these spleen cells despite an inability to generate anti-allogeneic or anti-TNP self CTL activity even in the presence of added T helper factors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occurring in a murine model of graft-vs-host disease. 295 40

A graft-vs-host (GVH) reaction of parental T cells in allogeneic F1 mice can lead to an autoimmune disease resembling human SLE. We analyzed the contribution of MHC genes to the development of IgG antinuclear antibody production and immune complex glomerulonephritis in MHC-congenic F1 recipients. DBA/2 T cells elicited IgG antibodies to histone, ssDNA, and dsDNA in all histoincompatible F1 recipients that were studied. The anti-DNA antibody responses were quantitatively similar among the F1 combinations and displayed comparable IgG2a subclass and cationic charge characteristics. In contrast, severe renal disease was manifested only in F1 mice that expressed H-2b encoded class II gene products. Disease susceptibility was associated with a decrease in circulating anti-DNA antibodies and a characteristic localization of immune complexes in the glomeruli. The data suggest that the production of potentially pathogenic IgG anti-nuclear antibodies is not sufficient for the development of renal disease in GVH-induced lupus. Thus, another event separate from autoantibody production is MHC dependent and appears to be critical for the formation and/or deposition of pathologic immune complexes.
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PMID:Allogeneic MHC antigen requirements for lupus-like autoantibody production and nephritis in murine graft-vs-host disease. 326 24


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