Diagnosis of autoimmune diseases.
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Autoantibodies↗
Biomedical subjects
P Druet
Publications and source records attributed to P Druet.
Susceptibility and resistance to autoimmunity following neonatal injection of semi-allogeneic spleen cells in rats.
A model of neonatal allotolerance was developed in rats. Brown-Norway (BN) neonates injected with semi-allogeneic (BN x Lewis) F1 hybrid spleen cells express a long-lasting chimerism and exhibit polyclonal B cell activation demonstrated by hyperimmunoglobulinemia affecting mainly IgE and IgG1, anti-laminin and anti-DNA autoantibodies as well as glomerulonephritis and anti-hapten antibodies. These abnormalities are autoregulated although the chimerism persists. In contrast, Lewis (LEW) neonates injected with semi-allogeneic (BN x LEW) F1 hybrid spleen cells exhibit a very short-lasting chimerism and transient activation of B cells, as reflected by increased allo-class II antigen expression, but do not develop an autoimmune disease. The autoimmune syndrome observed in BN rats is similar to that reported in mice during host-versus-graft reaction. Similarities between the drug-induced models of autoimmunity and allogeneic reactions in BN rats are also striking. The susceptibility of BN rats and the resistance of LEW rats to these autoimmune diseases might respectively reflect the involvement of TH2-like or of TH1-like subsets.
Animals↗
Adoptive transfer of experimental autoimmune uveoretinitis in HgCl2 injected rats.
We previously demonstrated that mercuric chloride (HgCl2) injected-(Lewis x Brown-Norway) F1 rats are protected against experimental autoimmune uveoretinitis (EAU) induced by active immunization with the retinal S-antigen (S-Ag). To better understand the mechanisms of the protection promoted by HgCl2, we studied the effect of HgCl2-induced autoimmune disease on transferred EAU. We demonstrate herein that HgCl2 has no effect on adoptively transferred EAU. Therefore, the HgCl2-induced autoimmune disease does not affect effector S-Ag specific T cells activated in vitro but acts at an earlier stage.
Animals↗
[role of cellular immunity in the genesis of rapidly progressive glomerulonephritis].
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Animals↗
[Extramembranous glomerulopathies].
Membranous nephropathy is defined by the presence of immune deposits localized on the epithelial side of the glomerular basal membrane. Its mechanism has been elucidated through numerous experimental models and is thought to be the consequence of in situ formation of immune complexes. Membranous nephropathy is clinically discovered by a nephrotic syndrome of unknown long-term evolution: 25% of the patients undergo complete spontaneous remission and 20% show progressive renal failure. As of today, no prognostic criteria are available. Numerous studies using steroids, immunosuppressive agents, or a combination of both, have tried to modify the natural history of the disease, but none of these protocols clearly seem to have changed the course of the disease.
Adrenal Cortex Hormones↗
HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. I. In vitro characterization of T cells involved.
Mercuric chloride (HgCl2) induces in Lewis (LEW) rats a non-antigen-specific immunosuppression and is able to down-modulate experimental allergic encephalomyelitis in about 70% of the rats. The aim of the present study was to determine the frequencies of lymph node cells involved in the proliferative response to myelin basic protein in rats injected with HgCl2 and immunized with myelin by using limiting dilution analysis (LDA). Highly frequent CD8+ T suppressor cells and at least 10-fold less frequent protein basic-specific T helper cells were detected in these rats. A third cell type allowing the proliferative response of Th cells in spite of Ts cells was also demonstrated. These cells, which could act as contrasuppressor cells, were CD4+ and adhered to Vicia villosa lectin; their frequency was in the same range as that of T helper cells. These data illustrate the potential role of different levels of T cell immunoregulatory activity in autoimmunity and the major interest of LDA in their analysis.
Animals↗
HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. II. In vivo demonstration of the role of T suppressor and contrasuppressor cells.
In the companion paper (J. Rossert et al., Cell. Immunol. 137, 1991), we showed by using limiting dilution analysis that Lewis (LEW) rats injected with HgCl2 and immunized with myelin (LEWHg/MYE) exhibit anti-basic protein CD4+ T helper cells (Th), at least 10-fold more frequent CD8+ T suppressor cells (Ts), and T contrasuppressor cells (Tcs). These Tcs cells were shown to be CD4+ T cells adhering to Vicia villosa (VV) lectin and allowed Th cells to proliferate despite the presence of Ts cells. The CD8+ Ts cells might be responsible for the protection from experimental allergic encephalomyelitis (EAE) observed in about 70% of LEW rats injected with HgCl2. The concomitant presence of CD4+ Tcs cells might explain that 30% of the rats escaped this protection. The aim of this work is to demonstrate in vivo the roles of CD8+ Ts cells and Tcs cells in mercury-induced protection from EAE. It will be shown that LEWHg/MYE rats depleted of CD8+ cells as well as LEWHg/MYE rats transferred with VV lectin-adherent Tcs cells develop EAE. These data demonstrate that CD8+ Ts cells are responsible for HgCl2-induced protection and that Tcs cells are involved in the control of Ts cells in vivo.
Animals↗
[Manifestation of immunologic origin produced by toxic compounds].
Toxic agents may induce immunological manifestations by interfering with either non specific or specific pathways of immunity. The interference with the specific pathways may result in stimulatory (autoimmunity or hypersensitivity) or suppressive reactions. Mechanisms responsible for autoimmunity of hypersensitivity are now better understood. Hypersensitive reaction may be the consequence of the recognition by T cells of the xenobiotic presented by MHC class II molecules. Mechanisms leading to autoimmune reaction probably differ according to the nature of the drug. Thus drugs metabolized by liver enzymes could induce autoimmune hepatitis as a consequence of the binding of a reactive metabolite to the enzyme, thus rendered immunogenic. Other drugs like thiol or metal-containing chemicals could be responsible for autoimmunity reaction by interacting with molecules involved in T-B lymphocyte cooperation. The knowledge of the involved mechanisms should allow to develop predictive assays.
Allergens↗
Effect of the thiol group on experimental gold-induced autoimmunity.
Brown Norway rats injected with aurothiopropanolsulfonate sodium salt develop systemic autoimmunity. The aim of this study was to assess the influence of the sulfur-containing group in this experimental model of gold-induced autoimmunity. It was shown that the sulfur-containing group does not induce autoimmunity of itself, but potentiates the immunotoxic effects of gold.
Animals↗
TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemically-induced autoimmunity.
Systemic autoimmune diseases can be induced experimentally in rodents by graft-versus-host or host-versus-graft reactions and by chemicals such as HgCl2, gold salts and D-penicillamine. These models share several features, such as productions of anti-nuclear antibodies, immune glomerulonephritis, MHC class II hyperexpression on B cells, hyper-IgE, increased IL-4 activity and impairment of IL-2 production. This profile of cytokines suggests a central role for TH2-type cells in their pathogenesis. Here, Michel Goldman and colleagues review the data supporting this hypothesis and discuss the possible molecular bases for T-cell activation in chemically-induced systemic autoimmunity.
Animals↗
Recurrent acute glomerulonephritis.
Biopsy-proven recurrent acute glomerulonephritis (AGN) is extremely rare and is usually seen in children with acute, well-defined streptococcal infections. We present here a patient with recurrent AGN in the absence of chronic bacterial infection. The subject, an 80-year-old man, had eight episodes of acute nephritic syndrome following upper respiratory tract infection. No abnormalities were detected during remissions. Renal biopsies during two of those episodes showed typical postinfectious acute exsudative endocapillary glomerulonephritis, while results of another biopsy performed during remission were normal.
Acute Disease↗
Experimental gold-induced autoimmunity.
The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown-Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity.
Animals↗
Increased expression of class II major histocompatibility complex molecules on B cells in rats susceptible or resistant to HgCl2-induced autoimmunity.
Administration of HgCl2 to the susceptible Brown-Norway (BN) rats induces an autoimmune disease characterized by a T-dependent polyclonal activation of B cells responsible for a dramatic increase in serum IgE concentration. The resistant Lewis (LEW) rats injected with HgCl2 do not exhibit such autoimmune manifestations. We show here that, upon HgCl2 injections, major histocompatibility complex (MHC) class II molecule expression is increased very early in lymph nodes and spleen B cells from both strains. So far, it is the earliest marker (day 3) of the effect of HgCl2 on the immune system. In both strains this enhancement is transient, but regulatory mechanisms are much more efficient in the resistant LEW strain than in the susceptible BN strain. In addition, we observed that MHC class II molecule expression on B cells differs according to the organ and the rat strain tested. All these findings are discussed in an attempt to underline the role of MHC class II molecule expression in the occurrence of mercury-induced autoimmunity.
Animals↗
Beneficial effect of human therapeutic intravenous immunoglobulins (IVIg) in mercuric-chloride-induced autoimmune disease of Brown-Norway rats.
Administration of HgCl2 to the susceptible Brown-Norway (BN) strain of rats induces an autoimmune disease characterized by polyclonal B cell activation, increased serum levels of IgE and the occurrence of anti-glomerular basement membrane antibody-mediated glomerulonephritis. We have observed that the simultaneous administration to BN rats of normal human polyspecific immunoglobulins for therapeutic use (IVIg) with HgCl2 significantly decreased the occurrence and severity of proteinuria, and reduced serum IgE levels in diseased animals. Hypergammaglobulinaemia was potentiated in animals receiving HgCl2 and IVIg, compared with animals receiving HgCl2 alone. In vitro experiments indicated that F(ab')2 fragments from IVIg inhibited the binding to laminin of pathogenic anti-laminin antibodies from diseased rats, as did antibodies from the resistant Lewis strain of rats but not antibodies from susceptible BN rats. These observations suggest that IVIg may interfere with the immune regulatory mechanisms involved in mercury-induced autoimmune disease in an analogous fashion to the ability of IVIg to suppress the expression of certain pathological autoimmune responses in humans.
Animals↗
Prevention of experimental autoimmune uveoretinitis and experimental autoimmune pinealitis in (Lewis x Brown-Norway) F1 rats by HgCl2 injections.
Mercuric chloride (HgCl2) induces in Brown-Norway (BN) and (Lewis x Brown-Norway) F1 hybrid rats a transient autoimmune disease characterized by the production of various antibodies to self and non-self antigens and by a dramatic increase of serum IgE. Experimental autoimmune uveoretinitis (EAU) can be induced in Lewis (LEW) and (LEW x BN) F1 hybrid rats by a single immunization with retinal S-antigen (S-Ag). Besides uveoretinitis, animals immunized with S-Ag develop an autoimmune pinealitis (EAP). We demonstrate in this study that (LEW x BN) F1 hybrid rats, injected with HgCl2 7 days before S-Ag immunization, are quite efficiently protected against EAU and EAP. We also show that HgCl2-induced protection is neither due to a cytotoxic effect of HgCl2 nor to CD8+ T-cell dependent mechanisms nor to the HgCl2-induced increase of serum IgE concentration. The role of other hypothetical mechanisms, such as anti-S-Ag anti-idiotypic antibodies and/or HgCl2-induced unbalance between T-helper cell subsets, is discussed.
Animals↗
[Immunosuppressive drugs and autoimmune diseases].
Only a few immunosuppressive drugs can be used today. These are: corticosteroids, azathioprine, cyclophosphamide, ciclosporine A, accessorily chlorambucil and methotrexate. They all have different actions on immune responses. The use of these drugs has completely changed the prognosis of autoimmune diseases such as systematic lupus erythematous, polyartheritis nodosa, Wegener's granulomatosis. Nevertheless treatment of other autoimmune diseases, such as type I insulin-dependent diabetes mellitus or multiple sclerosis, has been inconclusive.
Autoimmune Diseases↗
Chemical-induced autoimmunity.
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Animals↗
D-penicillamine-induced autoimmunity in Brown-Norway rats. Similarities with HgCl2-induced autoimmunity.
D-penicillamine (DP) has been previously shown to induce an autoimmune disease in Brown-Norway (BN) rats, characterized by a dermatitis, by the production of antinuclear antibodies, by the formation fo circulating immune complexes, and by linear IgG deposits along the glomerular basement membrane. These manifestations are quite similar to those observed in mercuric chloride (HgCl2)-induced autoimmunity. The mechanism of the latter disease has been recently partly elucidated. The aim of this study was to compare DP and HgCl2-induced autoimmunity in BN rats and to compare the mechanisms involved in both situations. A transient increase in the number of spleen cells, affecting B cells and CD4+ T cells, and an increase in serum IgE concentration, previously reported in HgCl2-induced autoimmunity, were observed during DP treatment. Autoreactive anti-class II T cells able to proliferate not only in the presence of autologous B cells but also in the presence of syngeneic normal B cells were found in DP-treated BN rats. Spontaneous regulation occurred, associated with the disappearance of autoreactive T cells. Suppressor CD8+ T cells were not involved in this phenomenon. Mechanisms involved in both the induction and the regulation of DP-induced autoimmunity seem to be quite similar to those reported in HgCl2-induced autoimmunity.
Animals↗